Hyoid bone malformation confirmed by 3-dimensional computed tomography

We describe the case of a young woman with pain on turning her head attributable to a malformation of the hyoid bone. Diagnosis was established using spiral computed tomography with the patient's neck in the position of greatest discomfort and with 3-dimensional reconstruction of the hyoid bone. Prior conventional radiography and magnetic resonance imaging did not aid in finding a diagnosis. After surgical removal of both greater cornua of the hyoid bone there was a complete relief of symptoms.     

Detection and characterization of the electron paramagnetic resonance-silent glutathionyl-5,5-dimethyl-1-pyrroline N-oxide adduct derived from redox cycling of phenoxyl radicals in model systems and HL-60 cells

Rapidly growing knowledge about the nature and behaviour of breast cancer has led to many treatment modalities. Consequently, the possibilities of individualizing the treatment of breast cancer increase. The major tool for the determination of an optimal treatment plan is the estimation of the extent of the disease: in other words, staging. As a consequence, together with the expected result of the treatment, the stage of the disease gives information on the prognosis of the patient. Current staging systems insufficiently describe the clinically important features of breast cancer with respect to management and outcome: local and regional extent, invasiveness, aggressiveness, the state of dissemination, and the effectiveness of different treatment modalities. For staging of the local and regional extent, histology plays a prominent role and should be incorporated in future staging systems. Histological workup therefore needs standardisation. Histological parameters as tumour size, grade, nodal status, and vascular invasion are also the most important prognostic factors. Many so-called biological prognostic factors are related to the invasiveness and aggressiveness (metastatic potential) of the tumour, and therefore to the prognosis of the patient. However, these factors do not necessarily predict the effectiveness of certain systemic treatments. Only if the biological foundation of a prognostic factor is completely clarified can treatment be based on this knowledge, and the factor will become a predictor for the treatment effect. Many "biological" prognostic factors do not fulfil this main criterion and are therefore not useful for clinical decision making. A clinically useful staging system covers three primary aims: (1) to guide locoregional treatment, (2) to prognosticate the chance of survival, and (3) to indicate who needs what kind of adjuvant treatment. For the conception of a new staging system the following steps should be taken: standardization of all aspects of histology, identification of regional nodal involvement, and validation of prognostic factors with respect to their predictive value to treatment outcome.     

Percutaneous bile duct drainage; experiences with a new type of endoprosthesis]

Self expandable stents were placed percutaneously in 105 patients with malignant biliary obstruction. Stent diameter was 1 cm; length, 3.5-10.5 cm. Of the 60 patients with common bile duct obstruction, 50 died 0.2-12 months (median 3 months) after stent insertion. Two patients developed recurrent jaundice and cholangitis after 6 and 12 months, respectively. One patient underwent reintervention. Ten patients, one after a successful reintervention, were alive without jaundice 1-8 months (median 5 months) after stent placement. Of the 45 patients with hilar lesions, 26 died 0.7-18 months (median 5 months) after stent placement, five of them with signs of cholangitis. Nineteen are alive 1-21 months (median 7 months) afterwards. Reinterventions were carried out in 13 patients (29%). The most common cause of stent malfunction was tumour overgrowth. Stent-related complications were seen in three patients.     

Cleavage motifs of the yeast 20S proteasome beta subunits deduced from digests of enolase 1

The 436-amino acid protein enolase 1 from yeast was degraded in vitro by purified wild-type and mutant yeast 20S proteasome particles. Analysis of the cleavage products at different times revealed a processive degradation mechanism and a length distribution of fragments ranging from 3 to 25 amino acids with an average length of 7 to 8 amino acids. Surprisingly, the average fragment length was very similar between wild-type and mutant 20S proteasomes with reduced numbers of active sites. This implies that the fragment length is not influenced by the distance between the active sites, as previously postulated. A detailed analysis of the cleavages also allowed the identification of certain amino acid characteristics in positions flanking the cleavage site that guide the selection of the P1 residues by the three active beta subunits. Because yeast and mammalian proteasomes are highly homologous, similar cleavage motifs might be used by mammalian proteasomes. Therefore, our data provide a basis for predicting proteasomal degradation products from which peptides are sampled by major histocompatibility complex class I molecules for presentation to cytotoxic T cells.     

Imbalance between interstitial collagenase and tissue inhibitor of metalloproteinases 1 in synoviocytes and fibroblasts upon direct contact with stimulated T lymphocytes: involvement of membrane-associated cytokines

OBJECTIVE: To determine whether direct cell-cell contact with stimulated T lymphocytes (a) differentially modulates the production of interstitial collagenase (matrix metalloproteinase 1 [MMP-1]) and tissue inhibitor of metalloproteinases 1 (TIMP-1) on human synoviocytes and dermal fibroblasts, and (b) induces the production of prostaglandin E2 (PGE2); and to identify the membrane-associated factors on T cell surfaces involved in these mechanisms. METHODS: Dermal fibroblasts and fibroblast-like synovial cells (synoviocytes) were cultured with fixed T cells, isolated plasma membranes from T cells, interleukin-1beta (IL-1beta; 250 pg/ml), or transforming growth factor beta (TGFbeta; 5 ng/ml). Culture supernatants were assayed for the production of MMP-1, TIMP-1, and PGE2. The expression of MMP-1 and TIMP-1 messenger RNA was analyzed by Northern blot of total fibroblast RNA. RESULTS: Membranes of stimulated T cells, i.e., human peripheral blood T lymphocytes (PBTL) and the human T cell line HUT-78, induced the production of PGE2 and MMP-1 on both synoviocytes and dermal fibroblasts. TIMP-1 production was enhanced upon contact with PBTL stimulated for short periods of time (2-4 hours) but not for longer periods. Similar results were obtained with CD4+ and CD8+ synovial tissue T cell clones (TCCs), which induced the production of TIMP-1 by fibroblasts when stimulated for short (2-4 hours), but not long, periods of time. This time dependency was not observed with HUT-78 cells. The production of MMP-1 by fibroblasts and synoviocytes upon cellular contact with stimulated T cells was higher than that induced by an optimum concentration of IL-1beta, whereas the production of PGE2 was equivalent or slightly lower. Cell membrane-associated IL-1alpha and tumor necrosis factor a, but not CD69, CD40 ligand, or CD11b, were involved in the induction of MMP-1 and PGE2 production, as shown by blockade experiments using monoclonal antibodies and cytokine antagonists. CONCLUSION: Synovial tissue TCCs and PBTL stimulated for long periods of time trigger the production of PGE2 and MMP-1, but not TIMP-1, in synoviocytes and dermal fibroblasts, thus inducing an imbalance between the metalloenzyme and its inhibitor. These results demonstrate that T cells may affect fibroblast and synoviocyte functions directly (i.e., by contact activation) and indirectly (i.e., by activation of cytokine production in monocyte/macrophages, which in turn, trigger stromal cell functions). Since the production of MMPs in monocyte/macrophages is also induced upon contact with stimulated T cells, our results strongly suggest that contact of synovial cells with chronically stimulated T lymphocytes favors matrix catabolism. By analogy, this mechanism may trigger tissue destruction in vivo and, thus, may potentiate tissue destruction in chronic inflammatory diseases such as RA.     

Expression of multiple apoptosis-regulatory genes in human breast cancer cell lines and primary tumors

Low molecular mass polypeptides (LMP) 2 and LMP7 and transporter associated with antigen processing (TAP) subunits TAP1 and TAP2 play a crucial role in antigen processing and cell surface expression of HLA class I molecules. Since monoclonal antibodies (mAb) to these molecules will facilitate the analysis of their expression, structure and function in normal and transformed cells, in the present study we have developed these reagents. Specifically anti-LMP2 and LMP7 mAb were generated from BALB/c mice immunized with specific peptides, and anti-TAP1 and TAP2 mAb from BALB/c mice immunized with respective recombinant proteins. mAb VF101-39F7 and VF101-39G5 were shown to be specific for LMP2, mAb VF103-5D5 and VF103-8C2 for LMP7, mAb VF108-1B3 and VF108-12D6 for TAP1 and mAb VF118-1E4 and VF118-2C5 for TAP2, since they reacted specifically with the corresponding immunogens in ELISA and with the corresponding LMP and TAP subunits when tested in Western blotting with human lymphoid cell extracts. Furthermore, the mAb immunoprecipitated components with the characteristic electrophoretic mobility from lymphoid cells. Both anti-LMP and anti-TAP mAb stained keratinocytes and infiltrating lymphocytes in frozen and formalin-fixed, paraffin embedded sections of normal skin in indirect immunoperoxidase reactions. Furthermore, all the mAb except mAb VF103-5D5 stained the cytoplasm of lymphoid cells in an intracytoplasmic staining reaction. The specificity and reactivity pattern of the mAb we have characterized indicate that they will be valuable reagents to analyze the cellular expression and tissue distribution of LMP and TAP subunits.     

Resolution of focal fatty infiltration of the liver

Focal fatty infiltration of the liver has been recognized as a distinct entity only since 1980. It may simulate neoplastic or other low-density parenchymal lesions, including abscesses and hemangiomas. I report a case of histologically confirmed focal fatty infiltration of the liver in a man with obesity and alcoholism; the lesion disappeared after the patient began a program of exercise, weight loss, and abstinence from alcohol. The possible pathogenesis of focal fatty infiltration of the liver is reviewed, diagnostic techniques are described, and reversibility of the lesion is discussed.