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  • 1
    ISSN: 1437-7772
    Keywords: Key words Humoral hypercalcemia of malignancy (HHM) ; Lung cancer ; Psoas abscess-like metastasis ; Parathyroid hormone-related protein (PTH-rP)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a patient with lung cancer associated with psoas abscess-like metastasis and humoral hypercalcemia of malignancy (HHM). A 71-year-old man was hospitalized with exacerbating pain on the left-side of his back and thigh. A computed tomography (CT) scan of the abdomen demonstrated a tumor in the left iliopsoas muscle, first diagnosed as psoas abscess. A chest roentgenogram showed right-sided pleural effusion, and CT scan of the chest demonstrated a tumor in the right lower lobe of the lung. His serum calcium level was 12.8 mg/dl, and parathyroid hormone-related protein (PTH-rP) level was elevated, to 11.1 pmol/l. The patient died of progressive disease, and necropsy specimens were diagnosed as poorly differentiated squamous cell carcinoma. Immunohistochemical staining for PTH-rP was positive in the tumor cells, including the primary and the metastatic lesions. A review of this unusual tumor type is also presented.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0827
    Keywords: Interleukin-1 ; Interleukin-1 receptor antagonist ; Estrogen ; Osteoporosis ; Cytokine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The recent finding that treatment with the interleukin-1 (IL-1) inhibitor, interleukin-1 receptor antagonist (IL-1ra) decreases bone loss and bone resorption in ovariectomized rats, strongly suggested that IL-1 mediates, at least in part, the effects of estrogen deficiency on bone resorption. Although in vitro studies have shown that IL-1 activates mature osteoclasts and stimulates osteoclastogenesis, the two main mechanisms by which estrogen deficiency stimulates bone resorption, it is still unclear whether IL-1 mediates both effects of estrogen deficiency in vivo. To investigate this matter, we have examined the changes in bone mineral density (BMD) which occur in ovariectomized rats after completion of 1 month of estrogen or IL-1ra treatment begun at the time of ovariectomy. Ovariectomy caused a marked decreased in BMD which was blocked by 17β estradiol and decreased by IL-1ra. Cessation of estrogen therapy was followed by a rapid induction of bone loss, indicating that estrogen blocks the activation and utilization of mature osteoclasts without depleting the bone microenvironment of osteoclast precursors and mature, inactive osteoclasts. In contrast, ovariectomized rats treated with IL-1ra maintained a stable bone density for the first 4 weeks after completion of the treatment. In these rats, bone loss resumed not earlier than 6 weeks after discontinuation of the IL-1ra treatment. Estrogen deficiency was necessary to unveil the bone-sparing effect of IL-1ra because in a control experiment in which rats were treated with IL-1ra for the 4 weeks before ovariectomy, BMD began to decrease immediately after ovariectomy. Based on these results we propose the hypothesis that in conditions of estrogen deficiency, the main effect of IL-1ra is to block the proliferation and differentiation of osteoclast precursors, an event that results in the depletion of mature, rapidly responsive osteoclasts. We also suggest that estrogen may have important direct effects on the regulation of osteoclast activity.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Histochemistry and cell biology 111 (1999), S. 7-12 
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  A rapid and simplified protocol for in situ hybridization (ISH) with polymerase chain reaction (PCR)-derived single-stranded DNA probes and S1 nuclease revealed transcripts of bone matrix proteins on decalcified skeletal bone specimens. Mouse bone tissue was fixed with 4% paraformaldehyde, decalcified with 20% EDTA, and embedded in paraffin. Each pair of primers for reverse transcriptase –PCR was designed to amplify a 280-bp DNA fragment from the coding region of the mature protein of mouse osteonectin (ON) and a 320-bp fragment from the coding region of mouse osteopontin (OP). Initial PCR products were eluted, purified, and reamplified by unidirectional PCR in the presence of the digoxigenin (DIG)-labeled dUTP. ISH was carried out by proteinase K treatment, hybridization, and washing. The unhybridized single-stranded DNA probe was selectively removed by S1 nuclease treatment. Hybridized probes were visualized with the alkaline phosphatase-conjugated anti-DIG antibody. The transcripts of ON and OP were clearly detected on the thin sections of the decalcified bone. Because this protocol does not require cloning or in vitro transcription, reliable and stable ISH can be done in an ordinary laboratory equipped with a thermal cycler.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Platelet-derived growth factor (PDGF), abundant in bone tissue, has been reported to stimulate mesenchymal cell proliferation and migration. To elucidate the functional roles of PDGF during fracture healing, we investigated the expression of PDGF-A and -B chain proteins and receptor α and β mRNAs in fractured mouse tibiae. Twelve-week-old male BALB/c mice were operated on to make a closed fracture on the proximal tibia. On days 2, 4, 7, 10, 14, 21, and 28 after the operation, the fractured tibiae were excised, fixed with 4% paraformaldehyde, decalcified with 20% EDTA, and embedded in paraffin to prepare 7-µm sections. Immunohistochemistry using polyclonal antibodies against human PDGF-A and -B chains was carried out by the avidin-biotin-peroxidase method. For in situ hybridization, we used digoxigenin-labeled single-stranded DNA probes specific for mouse PDGF receptors α and β generated by unidirectional polymerase chain reaction. In the inflammatory phase on days 2–4 after the fracture, mesenchymal cells gathering at the fracture site expressed the PDGF-B chain and β receptor mRNA. At the stage of cartilaginous callus formation on day 7, the immunoreactivity for PDGF-A and -B chains on proliferating and hypertrophic chondrocytes and the signals of α and β receptor mRNAs on proliferating chondrocytes became manifest. At the stage of bony callus and bone remodeling on days 14–21, the predominant expression of the PDGF-B chain and β receptor was observed on both osteoclasts and osteoblasts. On day 28, signals for PDGF ligand proteins and receptor mRNAs diminished. The coincidental localization of PDGF ligands and their receptors implies a paracrine and autocrine mechanism. Our data suggested that PDGF contributed in part to the promotion of the chondrogenic and osteogenic changes of mesenchymal cells from the early to the midphase of fracture healing; the functions mediated by the β receptor, including cell migration, might be prerequisites to the recruitment of mesenchymal cells in the initial step and to the interaction between osteoclasts and osteoblasts in the bone remodeling phase.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2307
    Keywords: Key words Sclerosing hepatic carcinoma ; Hypercalcaemia ; Parathyroid hormone-related protein (PTHrP) ; Immunohistochemistry ; In situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A 69-year-old man had a hepatic tumour occupying the left and half of the right lobe, with portal vein thrombus. There were hypercalcaemia and hypophosphataemia with increased nephrogenous cyclic adenosine monophosphate; bone metastases were excluded. Serum parathyroid hormone-related protein (PTHrP) was elevated, but no increase in intact parathyroid hormone (PTH) or vitamin D3 metabolites was found. At autopsy the histological features were typical of sclerosing hepatic carcinoma. By immunohistochemistry PTHrP was detected in cancer cell nests but not in the fibrous stroma. PTHrP transcripts were demonstrated by in situ hybridization using a polymerase chain reaction (PCR)-derived single-stranded DNA probe. Tumour cells expressed AE1 and CA19-9 (markers for cholangioepithelium) and CEA (for bile canaliculi). Electron microscopy revealed microvilli on the apical surface, and secretory granules 100 nm in diameter were observed. These findings indicate that this case is one of cholangiocellular sclerosing hepatic carcinoma. The interaction between cancer and stromal cells may be the cause of PTHrP overexpression.
    Type of Medium: Electronic Resource
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