Biomedical subjects
Publications and source records attributed to S Levi.
Pacing wire thrombosis may be invisible echocardiographically while producing severe symptoms. We report a patient whose pacing wire thrombosis presented as a pyrexial illness 5 months after its insertion. Treatment with tissue plasminogen activator provoked cardiovascular collapse; therefore, we recommend that such thrombosis be treated surgically.
In 1986, a retrospective survey was undertaken in the southern part of the province of Hainaut, Belgium, in order to measure the frequency of ultrasound examinations during pregnancy and to evaluate the effectiveness of the routine practice of echography screening for the detection of congenital malformations in an unselected population. The reference populations comprised 8316 pregnancies covered by the EUROCAT Registry of Hainaut. In 1986, 190 congenital malformations cases were registered. For each of the 190 cases, one control ending in the birth of a non-malformed infant was retrospectively selected. The analysis showed that an average of four ultrasound examinations were performed during pregnancy. When all malformations are considered, the sensitivity of the screening is 14% (27/190). Sensitivity of detection varied from 100% for gross malformations such as anencephaly to 0% for defects of a minor size such as facial clefts. In these 27 cases, obstetrical interventions following prenatal diagnosis were termination of pregnancy in 14 cases and induction of labor in 3 cases. Antenatal care was planned in 8 cases, 5 of which had early surgical repair. In the control group, a malformation was suspected in 3 of the 144 pregnancies (specificity of detection, 98%).
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The clinical course and results of drug treatment for manifestations of the carcinoid syndrome are reviewed in 63 patients. The five-year actuarial survival in this group of patients was 48 per cent. The only markers of a poor prognosis that could be identified at diagnosis were marked weight loss and a high (over 1000 mumol/day) 5-hydroxyindole acetic acid excretion. The relative effectiveness of well-established drugs that either block 5-hydroxytryptamine synthesis or block 5-hydroxytryptamine receptors is reported, with respect to the different manifestations of the syndrome, and compared with a small group of patients treated with long-acting somatostatin analogue. In over one-third of patients, primary tumours were not detected on initial investigation, and in none of these did symptoms referrable to the primary site become apparent later.
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Purified recombinant human heavy-chain (acidic) ferritin (rHF) was assessed in vivo in mice for effects on the proliferation (percentage of cells in S-phase) and absolute numbers of granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells in the femur and spleen and on the nucleated cells in the marrow, spleen, and blood. rHF significantly decreased cycling rates and absolute numbers of marrow and splenic hematopoietic progenitors and marrow and blood nucleated cellularity. These effects were apparent in BDF1, C3H/Hej and DBA/2 mice and were dose dependent, time related, and reversible. Suppressive effects were noted within three hours for progenitor cell cycling, within 24 hours for progenitor cell numbers, and within 48 hours for circulating neutrophils. Additionally, hematopoietic progenitor cells in DBA/2 mice infected with the polycythemia-inducing strain of the Friend virus complex (FVC-P) were insensitive to the in vivo administration of rHF. These studies demonstrate activity of rHF in vivo on myelopoiesis of normal but not FVC-P-infected mice. Since rHF suppresses hematopoietic progenitor cell proliferation from normal donors in vitro and from normal mice in vitro and in vivo but does not suppress progenitor cells from patients with leukemia in vitro or from mice with FVC-P-infection in vitro or in vivo, rHF may be useful as a candidate adjunct molecule for the protection of normal hematopoietic progenitor cells during chemotherapy.
To study the functional differences between human ferritin H- and L-chains and the role of the protein shell in the formation and growth of the ferritin iron core, we have compared the kinetics of iron oxidation and uptake of ferritin purified from human liver (90% L) and of the H-chain homopolymer overproduced in Escherichia coli (100% H). As a control for iron autocatalytic activity, we analyzed the effect of Fe(III) on the iron uptake reaction. The results show that the H-chain homopolymer has faster rates of iron uptake and iron oxidation than liver ferritin in all the conditions analyzed and that the difference is reduced in the conditions in which iron autocatalysis in high: i.e. at pH 7 and in presence of iron core. We have also analyzed the properties of two engineered H-chains, one lacking the last 22 amino acids at the carboxyl terminus and the other missing the first 13 residues at the amino terminus. These mutant proteins assemble in ferritin-like proteins and maintain the ability to catalyze iron oxidation. The deletion at the carboxyl terminus, however, prevents the formation of a stable iron core. It is concluded that the ferritin H-chain has an iron oxidation site which is separated from the sites of iron transfer and hydrolysis and that either the integrity of the molecule or the presence of the amino acid sequences forming the hydrophobic channel is necessary for iron core formation.
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A case of malignant somatostatinoma is reported in a patient with long-standing dermatitis herpetiformis and coeliac disease. The patient had non-specific abdominal pain of several years duration and came to attention because of weight loss despite strict adherence to a gluten-free diet. Plasma somatostatin levels were raised, and laparotomy showed a pancreatic tumour with metastases, which on histology, electron microscopy and immunohistochemistry proved to be a somatostatinoma. After a promising initial response to streptozotocin, she died 30 months later. This is the first reported occurrence of a somatostatinoma in a patient with coeliac disease, adding to the growing list of neoplastic complications in this condition.
Although nonsurgical alternative treatments for primary or retained common bile duct stones--such as dissolution of gallstones with deoxycholic acids and, especially endoscopic papillotomy--have become available, choledochoduodenostomy (CDS) has been used with increasing frequency over the past decade, with extension of the indications for its use. We report our experience with side-to-side CDS in 116 patients with benign (65 patients) and malignant (46 patients) biliary diseases. Even though the mean age of our patients with benign disease--patients who underwent urgent operations because of obstructive jaundice (74%), liver damage (approximately 60%), and other biliary complications--was 66.8 years, the perioperative mortality was 3.07% and the long-term follow-up results were excellent with no biliary complications. In regard to the controversy about the use of CDS in malignant biliary obstructions, our experience shows that none of the 42 patients had any complication due to malignant invasion of the stoma, and only one patient had ascending cholangitis; the perioperative mortality in this group was 8.6%. In our opinion, CDS is a relatively safe, definitive procedure for treatment of benign and malignant biliary diseases, with good long-term results in high-risk, aged patients.
Purified recombinant human ferritin composed solely of H subunit was radiolabeled and incubated with proerythroleukemic K562 human cells. A specific binding was detected, and it could be displaced only by ferritins, natural or recombinant, containing large proportion of the H subunit. The specific ferritin H-chain binding was saturable, and cells showed 17,000 to 23,000 binding sites per cell. The affinity constant measured at 37 degrees C was of 3 x 10(8) M-1. Treatment with pronase eliminated the specific binding. The binding sites were expressed in a high number during the cellular exponential phase of growth and progressively decreased to disappear when cells reached the plateau phase. Treatment of the cells with desferrioxamine increased recombinant H-ferritin binding, while iron had little effect. K562 cells induced to differentiate by hemin failed to bind ferritin H. Ferritin H-chain binding capacity is present on various cell lines such as HL60, lung cancer, and hepatoma cells. Analysis of the binding sites by western blotting showed a peptide with apparent mol wt of about 100 kd.
Nearly three-quarters of patients on long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) have small-intestinal inflammation, the consequences of which are largely unknown. Two potentially important complications, blood and protein loss from the small intestine, have been studied. 49 patients on NSAIDs underwent study with an indium-111 labelled leucocyte technique which localises and measures intestinal inflammation. 32 patients underwent simultaneous study with technetium-99m labelled red blood cells (RBC), which showed identical sites of localisation to 111In-leucocytes in 19. Intestinal blood loss was measured in 8 patients by use of chromium-51 labelled RBC, and a significant correlation between blood loss and intestinal inflammation was found. Intestinal protein loss was assessed in 9 patients with 51Cr-labelled proteins; patients with NSAID-induced small-intestinal inflammation were found to have a protein-losing enteropathy. These studies show that small intestinal inflammation caused by NSAIDs is associated with blood and protein loss, both of which may contribute to the general ill-health of rheumatic patients.
We used the monoclonal antibodies LFO3 (specific for the L subunit of ferritin) and 2A4 (specific for the H subunit) in an indirect immunofluorescence test for enumerating ferritin-bearing lymphocytes (FBL). In 13 normal subjects, the geometric mean value of FBL was 4% (range 0-13%) with the monoclonal antibody LFO3, and 3% (range 0-8%) with the monoclonal antibody 2A4. Values in 5 subjects with transfusional iron overload and increased plasma L-type ferritin concentration were 5% (4-7%) and 3% (2-4%), respectively, which is similar to those in normal subjects. Thirteen patients with malignant disease had normal to increased values for plasma ferritin; the circulating protein was largely of L-type with undetectable or very low concentrations of H-type ferritin. In the same patients, the percentage of FBL was greater with the monoclonal antibody 2A4 (geometric mean value 8%; range 3-12%) than with the monoclonal antibody LFO3 (geometric mean value 3%; range, 1-7%). It is concluded that acidic and basic isoferritins can be differently expressed on the surface of peripheral blood lymphocytes, and that the monoclonal 2A4 could be particularly useful in the measurement of FBL in patients with malignancy.
We have inserted the coding region of the cDNA for human ferritin H chain into the expression vector pEMBLex2. The plasmid obtained is able to direct the synthesis of the ferritin H chain in Escherichia coli up to a concentration of 15% of total soluble proteins. All expressed subunits are found correctly assembled in the complete ferritin molecule, which can be easily purified. We have shown that the ferritin synthesized in E. coli has an Mr, electrophoretic mobility, and thermal stability similar to natural human isoferritins and is recognized by monoclonal antibodies specific for the H, but not by those for the L human ferritin chains.
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Ferritin was purified from serum of patients with idiopathic haemochromatosis. Analysis on SDS electrophoresis showed that it is composed of two major bands of 19,000 and 23,000 Mr. The smaller peptide has an electrophoretic mobility and immunochemical reactivity similar to that of tissue L subunit. The larger, previously named G subunit, is recognized by concanavalin-A and by anti ferritin L-subunit, but not by anti-H, monoclonal antibodies. All of the antibodies show higher affinity for the L than for the G subunit. Therefore, the G chain appears immunochemically similar, but not identical, to ferritin L chain, and is responsible for serum ferritin binding concanavalin-A.
The ferritin present in human serum differs from the ferritins found in tissues and other body fluids in having negligible proportions of H subunits. This has been related to the possible presence of binding factors which would form complexes with H-subunit containing ferritins and thereby determine their rapid clearance and/or interference with immunoassays ('serum inhibition'). In this work we have tried to identify and characterize these binding factors. Dotting and blotting experiments demonstrated an interaction between tissue ferritins and human serum. This was stronger with human heart and recombinant H-type ferritin obtained from E. coli than with human liver ferritin. The serum binder appeared to be a glycoprotein migrating in the beta-2 region and with a molecular weight of about 200,000 and pI between 4 and 5. Two different approaches to purification of the ferritin-binding protein yielded enriched fractions containing also the complement proteins C3 and C4, the plasma protease inhibitor alpha-2-macroglobulin, and immunoglobulins. These in vitro findings may have physiological relevance.