Biomedical subjects
Publications and source records attributed to S Tomic.
We report a case of fibrosarcoma arising in the pineal of a 36-year-old female patient. She died at the age 43 following biopsy, radiation therapy, tumor resection, chemotherapy, and stereotactic radiosurgery. Light microscopic study of all tissues obtained, including immunohistochemistry and electron microscopy of surgically resected tumor and autopsied tissue revealed a slowly progressing primary fibrosarcoma.
Specific binding of transcription factors to DNA is crucial for gene regulation. We derived models for the binding specificity of transcription factors of the nuclear receptor family to DNA using two QSAR methods: a Free-Wilson-like method and COMparative BINding Energy (COMBINE) analysis. The analysis is based on experimental data for the interaction of 20 mutant glucocorticoid receptor DNA-binding domains with 16 different response elements in a total of 320 complexes (Zilliacus, J.; Wright, A. P.; Carlstedt-Duke, J.; Nilsson, L.; Gustafsson, J. A. Proteins 1995, 21, 57-67). The predictive abilities of the models obtained by the two methods are similar. The COMBINE analysis indicates that the most important properties for determining binding specificity for this dataset are the changes upon binding of the solvation free energies of the bases that are mutated in the dataset and the electrostatic interactions of the mutated nucleotides with certain charged amino acids. Further important descriptors are the changes of solvation free energy and surface area of the side chain of the mutated residue. It is clear, however, that there are additional features important for the specificity of binding that are not included in the models, such as differences in interfacial hydration of the complexes.
PURPOSE OF THE STUDY: The main cause of short metatarsal bones (commonly the fourth metatarsal) is premature closure of the distal epiphyseal plate. We report results of treatment of brachymetatarsia using the Ilizarov mini-fixator. MATERIAL AND METHODS: This study included 10 patients (19 feet) with a shortened fourth (18 feet) and third metatarsal bone. We performed gradual bone lengthening using the Ilizarov mini-fixator by distraction after osteotomy of the shortened metatarsal bone. RESULTS: Bone lengthening was effective (from 5 to 26 mm, mean lengthening 13 mm) almost without stepping out from the metatarsal formula. In terms of discomfort at walking, esthetic aspect of the foot, and shoe wearing, good clinical and cosmetic outcome was achieved. Pain as well as callosities on the plantar aspect of the foot disappeared in all patients. DISCUSSION: This technique of gradual distraction by callostasis gives sufficient lengthening for the treatment of brachymetatarsia. It overcomes the disadvantages of one-stage lengthening which include a small gain in length and neurovascular damage. This method could be recommended as the procedure of choice for solving the problem of brachymetatarsia.
Suppressors of cytokine signaling, SOCS-1, SOCS-2 and SOCS-3, are non-transmembrane proteins with Src-homology-2 (SH2) domain, involved in negative regulation of the Janus kinase (Jak)/signal transducer and activator of transcription (Stat) pathway. Using transient overexpression system the role of SOCS proteins in regulating prolactin receptor intracellular mediators leading to gene activation was analyzed. Overexpression of SOCS-1 led to a significant reduction in PRLR-mediated tyrosyl phosphorylation of Jak2, PRLR, Stat5 and the cytoplasmic protein tyrosine phosphatase SHP2. Overexpression of SOCS-3 however, led to selective inhibition in PRLR-mediated tyrosyl phosphorylation of Jak2, the PRLR as well as SHP2. On the other hand, overexpression of SOCS-2 had no inhibitory effects on the tyrosyl phosphorylation status of the PRLR, Jak2, Stat5 or SHP2 in response to PRLR activation. Finally, the role of SOCS proteins in regulating the biological activity of the PRLR was investigated. Unlike SOCS-2, both SOCS-1 and SOCS-3 abolished the ability of the PRLR to induce beta-casein gene promoter activation. These results demonstrate that SOCS-1, SOCS-2 and SOCS-3 are differentially implicated in PRLR signaling to gene activation.
The previously demonstrated functional and physical interaction of the SH2 domain protein-tyrosine phosphatase SHP-1 with the epidermal growth factor (EGF) receptor (Tomic, S., Greiser, U., Lammers, R., Kharitonenkov, A., Imyanitov, E., Ullrich, A., and Böhmer, F. D. (1995) J. Biol. Chem. 270, 21277-21284) was investigated with respect to the involved structural elements of SHP-1. Various mutants of SHP-1 were transiently expressed in 293 or COS-7 cells and analyzed for their capacity to associate with immobilized autophosphorylated EGF receptor in vitro and to dephosphorylate coexpressed EGF receptor in intact cells. Inactivating point mutation of the C-terminal SH2 domain reduced the association weakly, point mutation of the N-terminal SH2 domain reduced association strongly and the respective double mutation abolished association totally. The capacity of SHP-1 to dephosphorylate coexpressed EGF receptor was impaired by all point mutations. Truncation of the N-terminal or of both SH2 domains strongly reduced or abolished association, respectively, but the truncated SHP-1 derivatives still dephosphorylated coexpressed EGF receptor effectively. Various chimeric protein-tyrosine phosphatases constructed from SHP-1 and the closely homologous SHP-2 dephosphorylated the EGF receptor when they contained the catalytic domain of SHP-1. As native SHP-2, the chimera lacked activity toward the receptor when they contained the catalytic domain of SHP-2, despite their capacity to associate with the receptor and to dephosphorylate an artificial phosphopeptide. We conclude that the differential interaction of SHP-1 and SHP-2 with the EGF receptor is due to the specificity of the respective catalytic domains rather than to the specificity of the SH2 domains. Functional interaction of native SHP-1 with the EGF receptor requires association mediated by both SH2 domains.
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Gangliocytic paraganglioma (GPG) with local lymph node metastasis was found in the pancreas of a 74-yr-old female who presented with diarrhea, steatorrhea, vomiting, nausea, and abdominal pain. A Whipple procedure led to a complete resolution of these symptoms and a return of an elevated stomatostatin level to normal. This is the first description of GPG in this location and the first endocrinologically active GPG.
OBJECTIVE: To study neuroendocrine cells and nerves in vestibular glands of patients with vestibulitis. STUDY DESIGN: Substance P chromogranin, serotonin and neuron-specific enolase immunoreactivity was studied in vestibular gland tissue. Electron microscopic analysis was performed on vestibular duct tissue. RESULTS: Neuroendocrine cells containing immunoreactive serotonin and chromogranin were demonstrated in a vestibular gland duct of a patient with vestibulitis. Substance P immunoreactive axons were found in submucosal nerves, and rare, positively staining axons were seen in the duct epithelium. In another patient neuroendocrine cells with closely applied intraepithelial axons were demonstrated by electron microscopy in the duct of a vestibular gland. CONCLUSION: Intraepithelial axons are present in ducts of vestibular glands, where they are closely applied to serotonin-containing neuroendocrine cells. This close association and the presence of substance P immunoreactivity in local nerves may play a role in the symptomatology of vestibulitis.
One of alpha-RNP proteins (38 kDa alpha-protein) has been revealed as a target of the EGF receptor-associated protein kinase. A specific association of alpha-RNP complexes with the EGF receptor has been demonstrated. The involvement of alpha-RNP in the transduction of the EGF-induced signal has been suggested.
The SH2 domain protein tyrosine phosphatases (PTPases) PTP1C and PTP1D were found associated with epidermal growth factor (EGF) receptor which was purified from A431 cell membranes by several steps of chromatography. Both PTPases also associated with the EGF receptor upon exposure of immunoprecipitated receptor to lysates of MCF7 mammary carcinoma cells. The associated PTPases had little activity toward the bound receptor when it was autophosphorylated in vitro. Receptor dephosphorylation could, however, be initiated by treatment of the receptor-PTPase complex with phosphatidic acid (PA). When autophosphorylated EGF receptor was exposed to lysates of PTP1C or PTP1D overexpressing 293 cells, the association of PTP1C but not of PTP1D was enhanced in the presence of PA. In intact A431 cells, an association of PTP1C and PTP1D with the EGF receptor was detectable by coimmunoprecipitation experiments. PA treatment reduced the phosphorylation state of ligand activated EGF receptors in A431 cells and in 293 cells overexpressing EGF receptors together with PTP1C but not in 293 cells overexpressing EGF receptors alone or together with PTP1D. We conclude that PTP1C but not PTP1D participates in dephosphorylation of activated EGF receptors. A possible role of PA for physiological modulation of EGF receptor signaling is discussed.
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Merkel cell carcinoma of the genitalia is very rare and to date has been found only in vulvar mucosa. We describe an aggressive Merkel cell tumor in the frenulum of the penis with lymph node metastases, local recurrence, and eventually widespread dissemination. The primary tumor was associated with discontiguous squamous cell carcinoma in situ. This is the first report of Merkel cell (neuroendocrine) carcinoma in this anatomic site.
Malignant oncocytoma of the lacrimal sac is a rare tumor. A third example is presented here. In addition to oncocytes, tumor acini also harbored a few mucin cells and myoepithelial cells. The presence of immunoreactive lactoferrin and secretory piece suggested a resemblance to parotid acinic cell carcinomas. The difference was marked by a compact acinar structure and myoepithelial cell differentiation in the oncocytoma.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.