Biomedical subjects
Publications and source records attributed to I Samson.
A case of Langerhans cell histiocytosis in a 47-year-old male presenting as an aggressive appearing lesion of the clavicle is reported. It illustrates the difficulties of the radiological diagnosis of a solitary bone lesion.
Synovial chondromatosis is a rare lesion, which is still believed by most authors to be reactive rather than neoplastic. We report on a case of synovial chondromatosis with clonal chromosomal changes [43,XX,der (1) t (1;13) (p21-22;q21),-6,-13,-14, add(21) (q21)]. The presence of clonal chromosomal changes in this and in three previously reported cases suggests that synovial chondromatosis is a true neoplastic lesion.
We cytogenetically investigated six osteoid osteomas, one osteoblastoma and one aggressive osteoblastoma, and observed clonal structural changes in one osteoid osteoma and in the aggressive osteoblastoma. Clonal chromosome changes had not been reported previously in osteoid osteoma, whereas the only reported chromosome change in osteoblastoma was different from the one presented here.
A random pentapeptide library composed of 14 D-amino acids, including two unusual amino acids, thus representing 537,824 different peptide sequences anchored on polystyrene beads was created with each bead bearing a single pentapeptide sequence. This library was used for affinity screening against the fructose-1, 6-bisphosphate aldolase of Trypanosoma brucei labeled with biotin as well as versus the COOH-terminal labeled with fluorescein isothiocyanate. The thus selected peptide beads were identified and the appropriate sequences synthesized as peptide amides and evaluated for enzyme activity inhibition. Screening against the whole enzyme did not result in selection of an enzyme inhibitor. However, we demonstrate here that screening against a part of the enzyme involved in the catalytic activity may lead to the discovery of an enzyme inhibitor as well as an enzyme activator. Two low affinity inhibitors, RRVKF-NH2 and KThiKAR-NH2, with an IC50 of approximately 1 mM and approximately 0.2 mM, respectively, were identified. Two other pentapeptides with the sequence SWChaKK-NH2 and SKChaKM-NH2 are able to activate the enzyme fructose-1, 6-bisphosphate aldolase. Thus, successful screening of solid phase libraries can be accomplished using selected sequences of the target enzyme.
Human granulocyte chemotactic protein 2 (GCP-2) has originally been isolated from cytokine-stimulated osteosarcoma cells as a chemokine coproduced in minute amounts together with interleukin 8. Human GCP-2 (75 residues) was synthesized on a 0.25-mmol scale using Fmoc chemistry. After disulfide bridge formation and purification, monomeric GCP-2 was recovered as a 6-kDa protein; the pure synthetic protein showed a molecular mass of 8076 Da as determined by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The exact amino acid sequence of synthetic GCP-2 was confirmed by Edman degradation. Synthetic GCP-2 was an equally active (minimal effective concentration of 1-3 nM) chemoattractant for neutrophilic granulocytes as was natural 75-residue GCP-2. At concentrations up to 30 nM, synthetic GCP-2 did not stimulate eosinophil, monocyte, or lymphocyte chemotaxis. GCP-2 induced a dose-dependent increase in [Ca2+]i in neutrophils, 1 nM being the minimal effective concentration. The GCP-2-induced [Ca2+]i increase was completely prevented by pertussis toxin. Prestimulation of neutrophils with equimolar concentrations of purified natural IL-8, GROalpha, GROgamma and ENA-78 abolished the [Ca2+]i increase in response to 1 nM GCP-2. Alternatively, the [Ca2+]i rise induced by these CXC chemokines was inhibited by pretreatment of neutrophils with GCP-2. GCP-2 stimulated [Ca2+]i increases in CXCR1- and CXCR2-transfected cells, demonstrating that GCP-2 binds to both IL-8 receptors. Intradermal injection of synthetic GCP-2 resulted in a dose-dependent neutrophil accumulation and plasma extravasation in rabbit skin. To provoke this skin reaction, GCP-2 (10 pmol/site) was nearly as effective as IL-8, indicating that it is an important complementary mediator of the inflammatory response.
It is well established that the majority of myxoid/round cell liposarcomas (LPS) are characterized by a reciprocal translocation t(12;16)(q13;p11) which at the molecular level results infusion of the CHOP and FUS/TLS genes. It is assumed that functional characterization of these genes may provide insight into the molecular pathogenesis of this tumour type. This study describes two new cases of myxoid/round cell LPS having a t(12;22). By reverse transcription-polymerase chain reaction (RT-PCR) it has been shown that this leads to fusion between the CHOP and EWS genes, thus indicating involvement of the EWS gene, at least occasionally, in yet another sarcoma type. Combining these two cases with two others which were recently similarly characterized at the molecular level, their clinicopathological features have been compared with cases having the more usual t(12;16). It was not possible to identify any clinical or pathological differences between these molecular genetic subsets. The relevance or significance of these gene fusion products in myxoid/round cell LPS remains to be determined.
Schwannomas are relatively common, benign, peripheral nerve sheath tumours. They usually range in size from 2 to 20 cm, but when localised in the lower legs the maximum length is less than 10 cm. The case reported here was a giant fusiform schwannoma of the left fibular nerve with a length of 25.5 cm. In contrast to the usual findings of giant schwannomas, no cystic, haemorrhagic or necrotic changes could be found by ultrasonography, computed tomography or magnetic resonance imaging. The combination of tumour size, location and radiological presentation is very unusual and, to our knowledge, has never been reported before in the literature.
Inflammatory myofibroblastic tumor (inflammatory pseudotumor) is a pseudosarcomatous lesion that is recognized with increasing frequency in various anatomic locations. However, this lesion has not been previously reported in bone. We report on two cases of inflammatory myofibroblastic tumor occurring in bone in young adults. Both tumors presented as slightly painful, osteolytic, and well-delineated lesions of the distal femur, with a hyperintense signal on T2-weighted magnetic resonance imaging. The patients had an uneventful recovery after curettage. The follow-up time was 11 months for both patients, and no recurrence was noted. On histologic examination, the lesions were characterized by collagen-rich and generally poorly cellular tissue containing spindled to plump (myo)fibroblast-like cells and a variable admixture of inflammatory cells. Focal calcifications and reactive bone formation were present. Clonal, albeit different, chromosomal changes were found in both cases (47,XY,-9,-12,add(21)(q21),+der(?)t(?;9)(?;q11), +mar,+r and 47, XY, +r/47, idem, add(12)(p13)). The present and other reported cytogenetic findings suggest that inflammatory myofibroblastic tumors could well be neoplastic.
Primary malignant mesenchymoma of bone is a rare neoplasm consisting of two or more unrelated malignant mesenchymal components other than fibrosarcoma or malignant fibrous histiocytoma. The literature reports fewer than 15 cases, most of which were composed of osteosarcoma and liposarcoma. We report an exceedingly rare case of primary malignant mesenchymoma of bone composed of osteosarcoma and rhabdomyosarcoma (osteorhabdomyosarcoma), arising in the right proximal tibia of a 21-year-old woman. We review the literature and compare primary malignant mesenchymoma of bone with dedifferentiated chondrosarcoma and conventional intramedullary osteosarcoma.
OBJECTIVE: To determine the prevalence of positive tuberculin tests in a population of patients requiring long-term care in a hospital setting. DESIGN: Prevalence study: to evaluate reaction to the test among patients who agreed to be included in the study. SETTING: The study took place in two units of the Enfant-Jésus hospital where patients are admitted for chronic care. PARTICIPANTS: A total of 108 patients were eligible for the study; 56 agreed to take part. One patient died before the study was completed. INTERVENTIONS: The tuberculin test consisted of an injection of PPD-T and reading the reaction 48 to 78 hours later. A reaction > 10 mm was considered significant. Patients with insignificant reactions were injected again 2 weeks later in order to evaluate positive response secondary to reactivation of the immune system (booster effect). MAIN OUTCOME MEASURES: Indications of previous tuberculosis, risk factors for tuberculosis, immunosuppressive medication, length of stay in hospital, size of reaction. RESULTS: Seventeen tuberculin tests were positive (30.9%); of these, six were positive after the second injection. CONCLUSION: The prevalence of positive tuberculin tests was high in our elderly population; this finding is comparable to the findings of American studies.
The recently isolated full-length NADP-dependent isocitrate dehydrogenase (ICDH) cDNA encoding the tobacco cytosolic isoenzyme has been cloned into the expression vector pET8c and used to transform Escherichia coli strain BL21 (DE3). The recombinant protein was purified to electrophoretic homogeneity and used to raise polyclonal antibodies. Its kinetic properties were found to be identical to those of the cytosolic ICDH isoenzyme purified from tobacco cell cultures. The recombinant and the endogenous bacterial ICDH could be easily distinguished by their different behaviors during anion-exchange column chromatography and immunological response. An incomplete ICDH-encoding cDNA clone, encoding a protein lacking the first 36 amino acids at the N-terminus, was cloned into the expression vector pKK233-2 and used to transform ICDH-lacking E. coli cells (strain 2004). The truncated, recombinant ICDH produced by the bacteria was found to be inactive.
A case of therapy-related AML with t(8;16)(p11;p13) 14 months following the end of anthracycline-containing chemotherapy for a nonmetastatic osteosarcoma of the left tibia is presented. The patient was successfully treated with intensive remission-induction chemotherapy. Subsequently, he underwent an uncomplicated allogeneic bone marrow transplantation from his HLA-identical brother and is at present alive and disease-free 10 months after diagnosis of the secondary AML.
A synthetic peptide library, composed of 2.5 million L-amino acid pentapeptides anchored on polystyrene beads was prepared with each bead bearing a single pentapeptide sequence. This library was screened for interaction with glycosomal phosphoglycerate kinase (gPGK) of Trypanosoma brucei labelled with fluorescein or with biotin. Affinity beads that bound the enzyme were selected with a pipette or with streptavidin coated magnetic beads. The beads that bound to the enzyme were individually subjected to Edman microsequence analysis to determine the sequence of the corresponding peptide ligands. The corresponding peptide-sequences were synthesised as free peptide acids and evaluated for enzyme activity inhibition. The pentapeptide NWMMF was able to selectively inhibit gPGK with an IC50 of approximately 80 microM.
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A parosteal osteosarcoma of the distal femur with a typical radiographic and macroscopic appearance is reported. On histology the tumour was dominated by large numbers of osteoclast-like giant cells in a fibro-osseous background and islands of immature bone. Most of the neoplastic bone lacked osteoblastic rimming. There was no spatial relationship between the giant cells and areas of haemorrhage. Signs of 'dedifferentiation' were lacking. Cytogenetic a analysis revealed telomeric associations which are frequently found in giant cell tumours of bone. Parosteal osteosarcoma may, on histological appearances, hardly be recognizable as malignant. In addition, unusual changes such as abundant giant cells may be misleading in the absence of clinico-pathological correlation.
Three cases of extraskeletal myxoid chondrosarcoma with typical histologic and ultrastructural features were investigated cytogenetically. All three cases showed a reciprocal chromosome translocation characterized as t(9;22)(q22-31)(q11-12), thus confirming the findings in three previously karyotyped cases of extraskeletal myxoid chondrosarcoma in the literature. These data add significantly to the evidence of t(9;22) being diagnostic for extraskeletal myxoid chondrosarcoma. Other previously published cases with a range of complex karyotypes were less well defined morphologically. In cases with limited diagnostic material this karyotype might facilitate distinction from myxoid liposarcoma, which consistently shows t(12;16). Clear cell sarcoma, Ewing's sarcoma/primitive neuroectodermal tumor, and desmoplastic round cell tumor also show involvement of chromosome 22 with formation of a hybrid gene between the Ewing's sarcoma gene on band q12 and a transcription factor gene. Whether rearrangement of the Ewing's sarcoma gene is also present in extraskeletal myxoid chondrosarcoma is not clear at present. Cloning of the (9;22) translocation might provide important clues to the pathogenesis of this type of chondrosarcoma.
We report the cytogenetic findings of two cases of fibrous dysplasia, one occurring in the tibia, the other in the sphenoid. Both cases exhibited only one chromosome change: a t(6;11)(q15;p15) in the first case, a derivative chromosome 2 in the second. The previous cytogenetic report on fibrous dysplasia revealed only numerical changes. The significance of these inconsistent chromosomal findings in fibrous dysplasia is unclear.