[Current diagnostic strategy in pulmonary embolism].
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Biomedical subjects
Publications and source records attributed to J Roland.
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The following article is a report from the Chairman of the Professional Advisory Committee of the British Diabetic Association. The committee, with the help of a number of experts currently working in the field, produced a set of guidelines intended for use by health care professionals on the issues around genetic screening for Type 1 diabetes mellitus. The guidelines were approved by the Board of Management of the British Diabetic Association and we publish them here.
Polymorphonuclear neutrophils (PMNs) of patients with active Wegener's granulomatosis and PMN activated in vitro express elastase on their surface as detected by autoantibodies derived from patients with ANCA-positive vasculitis or chronic staphylococcus infections. The PMN-associated elastase was enzymatically active. By affinity-purified autoantibodies to elastase, the enzymatic activity was further enhanced as measured either by a chromogenic peptide or by elastin as substrate. Antibodies to human elastase from mouse or from sheep also enhanced elastase activity, whereas unrelated immunoglobulins had no effect. Taken together, our data indicate that autoantibodies to elastase are not inhibitory but upregulate the elastase activity and thereby might contribute to tissue damage.
We describe a combination of epithelial cell apoptosis and intracytoplasmic inclusions in prostatic epithelium in 6 patients who died from the acquired immunodeficiency syndrome. Two different types of apoptosis were detected: simple cell shrinkage and exploding glandular cells. No intracellular or extracellular viral particles were detected, either ultrastructurally or immunohistochemically. Intracytoplasmic inclusions are apoptotic bodies in a state of degradation and in close association with lipofuscin. The cell degeneration we observed confirms the theory that increased apoptotic cell depletion is responsible for weight loss in the acquired immunodeficiency syndrome. In the prostate itself, the combination of excessive apoptosis and active phagosomal digestion of apoptotic bodies presents a "human model" of postcastration rat ventral prostate, under the conditions of severe immune deficiency.
Primary lymphoma of the central nervous system, until recently representing about 1% of all brain tumours, shows a dramatically increased incidence in the general population as well as in high-risk groups (immunocompromised, AIDS), and may rise up to 6% in a population of AIDS patients. The clinical presentation is variable and cannot reliably be distinguished from other intracerebral tumours. At present, CT and MRI are the methods of choice for diagnosing cerebral lymphomas. However, their characteristics are not specific. The radiological picture may suggest glioma, meningioma, metastatic carcinoma or even a cerebrovascular accident. A labelled somatostatin analogue (pentetreotide) has been proposed as a new tracer for the imaging of somatostatin receptors, which have been identified by immunocytochemical or radioimmunoassay techniques in several organ systems. Somatostatin receptors were also identified in surgical biopsy samples from patients with Hodgkin and non-Hodgkin lymphoma and extracerebral lymphoma has already been visualised in vivo by means of In-111-labelled pentetreotide. While CT images of the brain showed a regression of the tumour after radiotherapeutic treatment, the scintigraphic images showed persistence of the tumoural tissue, corresponding with the clinical evolution and outcome. Furthermore, the absence of extra-cerebral lymphoma tissue, seen on the whole body images, was confirmed by post-mortem examination. To our knowledge, this is the first report of a primary intracerebral lymphoma visualised by means In-111-pentetreotide.
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The purpose of this paper is to present a pictorial display of osseous and articular lesions of the anterior chest wall. The role of CT and MR imaging in such disorders is emphasized. Imaging of the anterior thoracic wall by plain films is particularly difficult. However numerous disorders may be encountered. They include inflammatory hyperostosis and sclerosis of the clavicle and the sternum, condensing osteitis and post-traumatic osteolysis of the clavicle, radiation osteitis of the sternum and the ribs, septic arthritis of the sternoclavicular joint, primary and secondary tumors of the sternum and the ribs. We illustrate a spectrum of such lesions in which CT and MR imaging provides acute evaluation of both soft tissue and bone details.
We report a case of branchial cyst of unusual location. A asymptomatic 41-year-old man had a nontender deeply located left neck mass. Sonography, CT scan, and MRI showed a cystic lesion posterior to the sternocleidomastoid muscle. The diagnosis of branchial cyst much debated because of this atypical location was confirmed by histologic analysis after surgical resection. During organogenesis, the important caudal proliferation of the second branchial arch generates a transient cavity, the cervical sinus, which finally becomes obliterated. The incomplete obliteration of which can result in a sinus, fistula or cyst. Such cysts typically lie at the level of the mandibular angle, anterior to the sternocleidomastoid muscle. This location has been regarded as a major diagnosis criteria, but it is not absolute. The sternocleidomastoid muscle develops apart from the branchial apparatus, caudally and anteriorly. As a result the cysts which are located on an inferior portion of the cervical sinus can lie posterior to this muscle.
An enzyme immunometric assay of thyroliberin (TRH) using monoclonal antibodies and a derivatization procedure is described. This assay, named SPIE-IA, involves a four step procedure after chemical derivatization of TRH and biological samples by diazotized APEA. Step 1: derivatized TRH was immunocaptured by a monoclonal anti-TRH antibody coated on a 96-well microtiter plate. Step 2: after washing, derivatized TRH was cross-linked via its amino group to the wells using glutaraldehyde. Step 3: washing and treatment with NaOH. Step 4: measurement of bound TRH using a monoclonal anti-TRH antibody labeled with acetylcholinesterase. The minimal detectable concentration was 0.1 pmol/ml: with a coefficient of variation less than 10% in the 0.156-10 pmol/ml range. This assay is 26-fold more sensitive and more specific than the competitive enzyme immunoassay using the same monoclonal capture antibody, derivatized TRH and TRH-acetylcholinesterase conjugate as tracer. Good correlation was observed between SPIE-IA and a sensitive competitive enzyme immunoassay using polyclonal antibodies.
In one transgenic strain harboring a human c-myc proto-oncogene construct, the transgene was actively and exclusively expressed in the thymus, where it contributed to the development of lymphoma that corresponded to CD4(+)CD8(+) cells. Here, we have pursued the analysis of transgene expression in healthy transgenic mice and show that transgene activation occurs in the thymus 3 days before birth, at a time when CD4(+)CD8(+) lymphocytes emerge. In the adult, its expression is restricted to the CD4(+)CD8(+) cells. The region flanking the transgene insertion site was isolated and made it possible to map the preintegration locus, hereafter called Tsil (for thymus-specific integration locus) on chromosome 17 between D17Rp11e and Ras12-3. A YAC that contains both Tsil and the Pim2 locus, previously shown to be involved in progression of T-cell lymphoma, was isolated. Analysis of Tsil offers a unique opportunity to identify a regulatory region or a gene that might play an important role in T-cell maturation.
Clinical and experimental observations indicate that the motility of the oesophagus may be affected by emotional stimuli. The aim of this study was to evaluate the incidence of oesophageal contractility impairment in patients suffering from a psychiatric disorder. Fifty-one patients admitted to the psychiatric department were submitted to an oesophageal transit study by means of krypton-81m. All patients with an abnormal oesophageal transit underwent manometry and endoscopy. The level of depression and anxiety was evaluated by the treating psychiatrist, using the Hamilton Depression and Anxiety Rating Scales. The oesophageal transit was abnormal in 13 patients. Two of these 13 patients refused manometric investigation. In ten of the 11 remaining patients, the manometry revealed functional motor abnormalities. Endoscopy, performed in all these ten patients, was normal. In conclusion, a high percentage of oesophageal contractility disturbances was found in psychiatric patients complaining of anxiety and/or depression. These abnormalities were detected by scintigraphy as well as by manometry. Owing to the normal endoscopic findings, these contraction abnormalities are likely to reflect a functional motor impairment.
The pons is covered by a rich venous network offering numerous vascular landmarks in MRI and during surgery. We present an original study of the veins as they appear on MR multiplanar scans after gadolinium IV injection. This prospective study is based on 40 consecutive patients with normal posterior fossa structures. One of the major venous collectors follows the pons: the superior petrosal v. was identified on MRI in 95% of our cases. Its hooklike extremity drains into the superior petrosal sinus. The inferior petrosal v. was never identifiable. The superficial pontine venous network are identified in 72.5% of cases in the axial plane and were organised in longitudinal and transverse collectors, whose MR aspects are presented here.
Magnetic resonance imaging (MRI) has progressively become the major or even the only imaging procedure for displaying the vascular relationships of the brainstem in the context of infra-tentorial lesions. In order to assess the MR sectional anatomy of the bulbar vv. 40 normal patients were examined in the MR axial, frontal and sagittal planes after gadolinium i.v. injection. The bulbar venous networks were inconstantly visualised: anterior vv. (16%). posterior (3%), lateral (8%). The vein of the lateral recess of the fourth ventricle was constant in the three planes; the inferior petrosal sinus could be seen in 82% of cases. Their relation with the posterior fossa structures are emphasised and discussed.
Whether antibodies to elastase (EL) exist in autoimmune disease is controversial, due in part to inadequate methods used to determine antibody titers. We have developed a highly sensitive and specific enzyme-linked immunosorbent assay, using immobilized EL and mouse monoclonal antibodies for standardization. The specificity of the enzyme-linked immunosorbent assay was confirmed by absorption studies and Western blot analysis. Using this enzyme-linked immunosorbent assay, antibodies to EL were found in antineutrophil cytoplasmic antibody-positive vasculitis patients to a higher degree than reported in the literature (in eight of 108 patients with Wegener's granulomatosis and in 15 of 78 patients with microscopic polyangiitis). Patients with Wegener's granulomatosis or microscopic polyangiitis and antibodies to EL had significantly more severe renal involvement, as indicated by the higher frequency of dialysis dependency. Also in contrast to reported data, antibodies to EL were found less frequently in patients with systemic lupus erythematosus (nine of 64 patients). Binding of systemic lupus erythematosus sera to uncoated plates, giving a nonspecific reaction, was seen quite frequently, which might explain the discrepancy.
We address the mechanism of hybrid resistance (HR) in vitro using NK effector cells and target lymphoblasts from H-2b, H-2d, and H-2b/d mice. The 5E6 (Ly49C)+ subset of F1 NK cells lyse BALB/c (H-2d) but not B6 (H-2b) targets unless either anti-5E6 or anti-H-2Kb MAbs are present. H-2Dd transgenic B6 (D8) targets are not susceptible to F1 Ly49A+ effectors. Furthermore, 5E6+ Ly49A+ F1 effectors lyse B6 and BALB/c targets only in the presence of anti-5E6 and anti-Ly49A MAbs, respectively. Thus, recognition of H-2Kb by 5E6 and H-2Dd by Ly49A transduce independent inhibitory signals. Moreover, anti-5E6 MAbs enable 5E6+ BALB/c NK cells to lyse (BALB/c x B6)F1 targets. These data support the "missing self" and not the "hemopoietic histocompatibility antigen" hypothesis for HR. In addition, 5E6+ NK cells from BALB/c and BALB.B, but not B6 or (BALB/c x B6)F1, mice receive negative signals from both H-2d and Kb class I antigens. Thus, allelic differences in 5E6 (C57BL versus BALB) may regulate recognition events by NK cells.
Increased hepatic uptake and absent bone marrow uptake on bone marrow immunoscintigraphy has been reported after the formation of human antimurine antibodies. A case of generalized bone marrow metastases is presented, in whom an elevated liver uptake on bone marrow immunoscintigraphy proved to be associated with extramedullary hematopoiesis. Extramedullary hematopoiesis should be included as a possible cause of a disproportionately elevated liver uptake on bone marrow immunoscintigraphy, especially on initial studies, or on repeat studies with low human antimurine antibody titers. Tc-99m labeled BW 250/183 immunoscintigraphy may aid in the localization of suspected sites of extramedullary hematopoiesis.
We have previously shown that the steady-state level of c-myc mRNA in vivo is primarily controlled by posttranscriptional regulatory mechanisms. To identify the sequences involved in this process, we constructed a series of H-2/myc transgenic lines in which various regions of the human c-MYC gene were placed under the control of the quasi-ubiquitous H-2K class I regulatory sequences. We demonstrated that the presence of one of the two coding exons, exon 2 or exon 3, is sufficient to confer a level of expression of transgene mRNA similar to that of endogenous c-myc in various adult tissues as well as after partial hepatectomy or after protein synthesis inhibition. We now focus on the molecular mechanisms involved in modulation of expression of mRNAs containing c-myc exon 2 sequences, with special emphasis on the coupling between translation and c-myc mRNA turnover. We have undertaken an analysis of expression, both at the mRNA level and at the protein level, of new transgenic constructs in which the translation is impaired either by disruption of the initiation codon or by addition of stop codons upstream of exon 2. Our results show that the translation of c-myc exon 2 is not required for regulated expression of the transgene in the different situations analyzed, and therefore they indicate that the mRNA destabilizing function of exon 2 is independent of translation by ribosomes. Our investigations also reveal that, in the thymus, some H-2/myc transgenes express high levels of mRNA but low levels of protein. Besides the fact that these results suggest the existence of tissue-specific mechanisms that control c-myc translatability in vivo, they also bring another indication of the uncoupling of c-myc mRNA translation and degradation.
Immunoreactivity for B and SP was detected by means of light and electron microscopy (by preembedding immunocytochemistry), in eosiniphilic polymorphonuclear leukocytes infiltrating the connective tissue of gastrointestinal and respiratory tract in mouse, rat and human ; and in human bronchoalveolar lavages in case of hypereosinophilia. This positive reaction depends on the use of an acetic-acid-containing-fixative (minimum 48 hours), and is located in the granules of eosinophils at their membrane level, and on eosinophil plasma membranes. Eosinophil peroxidases (catalases) should not affect the immunocytochemical reaction, since heating during a paraplast embedding and sodium-azide in electron microscopy procedure destroyed these enzymes. The membrane-bound immunoreaction for B and SP, with very close structural similarity, suggested cross-reactivity between the two neuropeptides, with recognition of one or several epitopes by the polyclonal antisera. One of these epitopes is probably associated with the C-terminal sequence of B (with tachykinin-like activity) and seems to be present in other neuropeptides such as SP ; another epitope would be the N-terminal sequence of SP (with bradykinin-like activity). Hence, eosinophils could be the source of tachykinin and bradykinin. Another hypothesis about the membrane immunolocalization (as yet unproved experimentally) would be a cross-reactivity due to recognition of electron-negative charges of membrane phospholipides. Lysophosphatidic acid could play a hormone-like activity and mimic B and SP activities, such as growth factors. Finally, anti-B and anti-SP antisera could contain anti-idiotype antibodies uncovering receptors. In conclusion : eosinophils might produce neuropeptides or neuropeptide-like substances, with, for instance, bronchoconstrictive activity by paracrine control and possible complementarity with nerve endings.