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Biomedical subjects

P Papadopoulos

Publications and source records attributed to P Papadopoulos.

At least 37 records · Page 2Linked to original sources

Polymorphism in a ferritin H gene from chromosome 6p.

This paper addresses the question of whether abnormalities in ferritin expression in the iron storage disease hemochromatosis (HC) involve major deletions or alterations in regions containing the two ferritin H genes that lie near the disease locus on chromosome 6p. We present evidence from analyses of Southern blots that neither gene is deleted in hemochromatosis. We also describe a polymorphism in one of the genes that we have previously shown to be a processed pseudogene. This polymorphism does not correlate with the presence of HC. The PIC value for this polymorphism was calculated as 0.49.

Blotting, Southern↗

Identification of two human ferritin H genes on the short arm of chromosome 6.

We have found by analyses of human-hamster hybrid cells that two human ferritin H genes lie near the locus of the iron storage disease idiopathic hemochromatosis on chromosome 6p. One of these genes was isolated and shown to be a processed pseudogene. Comparison of its sequence with those of other ferritin H pseudogenes indicates that they may be derived from a functional H gene other than that on chromosome 11.

Animals↗

Ferritin H gene polymorphism in idiopathic hemochromatosis.

The authors studied the H ferritin restriction polymorphism in 83 hemochromatosis patients and 84 controls as well as in 19 nuclear families. No significant difference was found with the ten restriction enzymes used (HindIII, EcoRI, EcoRV, PvuII, BamHI, PstI, Bg/I, Bg/II, HincII, and TaqI). Hence, the genomic abnormality responsible for idiopathic hemochromatosis is not a major deletion of an H ferritin gene. A higher frequency of one HindIII fragment, although nonsignificant when the number of comparisons made is taken into account, was observed in the patients. This HindIII fragment hybridizes with the H ferritin probe and with a 28 S ribosomal probe, and its segregation with HLA haplotypes (hence its assignment to chromosome 6) is uncertain. Its possible meaning in the expression of the disease is discussed.

Chromosome Mapping↗

Continuous electrocardiographic monitoring in patients with unstable angina pectoris: evaluation of medical treatment.

Sixteen patients under treatment for unstable angina (UA) were subjected to 24-hour Holter monitoring after having been asymptomatic for at least 12 hours. 12-lead ECGs were obtained every 4 hours and when anginal pain supervened. Six patients (37.50%) had no evidence of ischemia in the Holter recordings and in the 12.lead ECGs and reported no anginal pain; five (31.25%) reported no pain but had evidence of ischemia in the Holter recordings and five (31.25%) reported anginal pain and had evidence of ischemia both in the Holter recordings and in the 12-lead ECGs. The probability for a 12-lead ECG to record an episode of silent myocardial ischemia (SMI) was only 1.54 x 10(-5). Medical treatment using conventional criteria was successful in 11 patients (68.75%). If the results of Holter monitoring are considered, the success rate was 37.50% (6 out of 16 patients free from ischemia). We conclude that as Holter monitoring reveals the episodes of SMI, it is a better means for assessing the results of medical treatment.

Adult↗

Cloning, characterization, expression, and chromosomal localization of a human ferritin heavy-chain gene.

A genomic phage clone containing a full-length copy of a functional human gene for ferritin heavy chain has been isolated. The gene consists of four exons spanning approximately 3 kilobases and has been localized to chromosome 11. The functionality of the gene was demonstrated by the fact that both transient transfectants and stable transformants of murine fibroblasts actively transcribe human ferritin heavy-chain mRNA.

Amino Acid Sequence↗

Serum beta 2 microglobulin in malignant lymphoproliferative disorders.

Serum beta-2-microglobulin (S-beta 2M) was measured at diagnosis in 44 patients with lymphocytic leukemias and 47 with malignant lymphomas. Among patients with chronic lymphocytic leukemia (CLL) S-beta 2M was raised (greater than 3 mg/l) in 74% and in 23.5% of those with acute lymphoblastic leukemia (ALL). The frequencies for non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) were 59.2% and 40%, respectively. In CLL patients high serum values correlated with large tumor mass, as estimated by Rai's clinical criteria (P less than 0.001), by total peripheral lymphocytes (r = 0.41, P less than 0.05) and by the percentage of bone marrow infiltration of the lymphocytes (P less than 0.01). A significant relation was also found in CLL patients between S-beta 2M level and survival (P less than 0.05). In ALL no association was found between S-beta 2M level with peripheral lymphoblast concentration, French-American-British (FAB) subclassification, splenomegaly, and survival. In NHL patients a significant association was found between S-beta 2M levels and stage of disease (P less than 0.01) and an obscure relation (P less than 0.1) with the presence of lymph nodes greater than 3 cm in diameter, splenomegaly, and hepatomegaly. No significant association was found between S-beta 2M level and histologic subtypes, presence of B symptoms, bone marrow involvement, and survival. In HD patients a significant association was found between the level of S-beta 2M and stage of disease (P less than 0.05) and presence of splenomegaly (P less than 0.05). No association was found between S-beta 2M level and histologic subtypes, lymph nodes greater than 3 cm in diameter, bone marrow involvement, and B symptoms. A significant relation was found between S-beta 2M level and survival in HD patients with widespread disease (P less than .025).

Hepatomegaly↗

Immunochemical evidence for extensive ligand-induced conformational changes in Lactobacillus casei dihydrofolate reductase.

The effects of ligand binding on antibody complex formation of Lactobacillus casei dihydrofolate reductase have been investigated. Binary complexes containing either substrate and inhibitors or NADP+ and NADPH together with ternary complexes containing inhibitors and coenzyme were examined. Whereas substrate and inhibitor binding alone show no effect, the binding of coenzyme reduces antibody complex formation. The most striking effect is observed with ternary complexes containing methotrexate or aminopterin and NADPH: maximal retention of the labeled protein in the immunoprecipitation assay is reduced to approximately 30% of its original value with dihydrofolate reductase alone due to a decrease in both the affinity and lifetime of the antibody-protein complex at one or more antigenic sites. This result is discussed in terms of different conformational changes brought about by NADP and NADPH.

Animals↗

In vitro strain distribution in the proximal tibia. Effect of varus-valgus loading in the normal and osteoarthritic knee.

Six human cadaver legs were tested with strain-gauge rosettes to determine the effects of varus/valgus loading on the distribution of strain on the cortical bone of the proximal tibia at loads of up to 250 kg. Changes in the femorotibial angle of 1.5 degrees and 3.1 degrees, to create varus/valgus deformities, produced significant unloading of the opposite aspect of the normal leg. A varus deformity of 3.1 degrees in the medial compartment osteoarthritic model virtually unloaded the lateral compartment and, because of the bending effect, placed the whole of the lateral aspect of the leg into axial tension. Under these conditions, the axial strains in almost the whole of the medial aspect of the tibia were doubled, from an initial value of 250 microstrain (compressive) to a value of approximately 500 microstrain (compressive). While a change in load-action, to simulate a 3.1 degrees valgus deformity in the medial compartment osteoarthritic model, did not completely unload the medial plateau of the tibia, it was suggested that such unloading could be achieved with slightly greater valgus loading. Successful clinical results, employing valgus osteotomies in patients with medial compartment osteoarthritis, are obtained by unloading the medial compartment while markedly increasing compressive loads on the whole of the lateral aspect of the leg.

Adolescent↗

The effect of medial meniscectomy on strain distribution in the proximal part of the tibia.

The tibiae of five fresh adult human cadaver legs (amputated proximal to the knee) were instrumented with twenty-five strain-gauge rosettes and were tested in axial compression, simulating single-limb stance, at loads of as much as 2450 newtons. We compared the status of the normal knee, with menisci intact, with the status of the same knee after partial or total medial meniscectomy. The resultant changes in strain on the cortical bone of the tibia indicated that medial meniscectomy caused reduced compressive strains on the whole of the lateral aspect of the tibia, while on the medial aspect compressive strains were increased at all levels beyond seventy millimeters distal to the joint-line; however, within fifty millimeters of the joint-line on the medial aspect, there was a significant reduction of compressive strains.

Adolescent↗

Rocking motion of the right cardiac cavities in Ebstein's anomaly. A specific cineangiographic sign.

In 7 cases of Ebstein's anomaly the right cineangiogram disclosed a big right atrium, the tricuspid valve positioned to the left of the spine and tricuspid regurgitation. The right atrial appendage was nearing the outflow tract of the right ventricle and the pulmonary artery so as the normal U appearance of the right aniograms was abolished. In addition to these signs a very characteristics and almost pathognomonic rocking motion of the radiopaque material, moving from the right atrium towards the right ventricle during ventricular diastole and backwards to the atrium during the next ventricular systole was observed. This sequence of motion gives the impression of a rocking hammock or pendulum.

Angiocardiography↗