GLORIA

GEOMAR Library Ocean Research Information Access

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Publication Date: 2015-02-14
    Description: Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD) sit at opposite ends of a clinical spectrum caused by mutations in the extracellular matrix protein collagen VI. Bethlem myopathy is relatively mild, and patients remain ambulant in adulthood while many UCMD patients lose ambulation by their teenage years and require respiratory interventions. Dominant and recessive mutations are found across the entire clinical spectrum; however, recessive Bethlem myopathy is rare, and our understanding of the molecular pathology is limited. We studied a patient with Bethlem myopathy. Electron microscopy of his muscle biopsy revealed abnormal mitochondria. We identified a homozygous COL6A2 p.D871N amino acid substitution in the C-terminal C2 A-domain. Mutant α2(VI) chains are unable to associate with α1(VI) and α3(VI) and are degraded by the proteasomal pathway. Some collagen VI is assembled, albeit more slowly than normal, and is secreted. These molecules contain the minor α2(VI) C2a splice form that has an alternative C terminus that does include the mutation. Collagen VI tetramers containing the α2(VI) C2a chain do not assemble efficiently into microfibrils and there is a severe collagen VI deficiency in the extracellular matrix. We expressed wild-type and mutant α2(VI) C2 domains in mammalian cells and showed that while wild-type C2 domains are efficiently secreted, the mutant p.D871N domain is retained in the cell. These studies shed new light on the protein domains important for intracellular and extracellular collagen VI assembly and emphasize the importance of molecular investigations for families with collagen VI disorders to ensure accurate diagnosis and genetic counseling.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2016-07-06
    Description: Background Endoplasmic reticulum (ER) stress results from protein misfolding imbalance and has been postulated as a therapeutic strategy. ER stress activates the unfolded protein response which leads to a complex cellular response, including the upregulation of aberrant protein degradation in the ER, with the goal of resolving that stress. O 6 -methylguanine DNA methyltransferase (MGMT), N -methylpurine DNA glycosylase (MPG), and Rad51 are DNA damage repair proteins that mediate resistance to temozolomide in glioblastoma. In this work we sought to evaluate whether ER stress-inducing drugs were able to downmodulate DNA damage repair proteins and become candidates to combine with temozolomide. Methods MTT assays were performed to evaluate the cytotoxicity of the treatments. The expression of proteins was evaluated using western blot and immunofluorescence. In vivo studies were performed using 2 orthotopic glioblastoma models in nude mice to evaluate the efficacy of the treatments. All statistical tests were 2-sided. Results Treatment of glioblastoma cells with ER stress-inducing drugs leads to downregulation of MGMT, MPG, and Rad51. Inhibition of ER stress through pharmacological treatment resulted in rescue of MGMT, MPG, and Rad51 protein levels. Moreover, treatment of glioblastoma cells with salinomycin, an ER stress-inducing drug, and temozolomide resulted in enhanced DNA damage and a synergistic antitumor effect in vitro. Of importance, treatment with salinomycin/temozolomide resulted in a significant antiglioma effect in 2 aggressive orthotopic intracranial brain tumor models. Conclusions These findings provide a strong rationale for combining temozolomide with ER stress-inducing drugs as an alternative therapeutic strategy for glioblastoma.
    Print ISSN: 1522-8517
    Electronic ISSN: 1523-5866
    Topics: Medicine
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 27 (2002), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Cutaneous metastases from internal malignancies or primary skin cancers are uncommon, and a zosteriform pattern is very rare. Histologically, these cutaneous metastases usually appear as malignant epithelial cells located throughout the dermis or subcutaneous fat and without connection to the overlying epidermis. The presence of melanocytes in such lesions is atypical. Moreover, although zosteriform cutaneous metastases of cutaneous squamous cell carcinoma have previously been described in immunosuppressed patients, they have not been reported in immunocompetent patients. We report an unusual case of a woman with cutaneous hyperchromic zosteriform metastases, clinically mimicking a metastatic melanoma but appearing histologically as epidermotropic and pigmented metastases of a cutaneous squamous cell carcinoma.
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 30 (2005), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Matrix metalloproteinases (MMP)-2 and -9 have been implicated in malignant tumour progression, partly because they degrade collagen type IV, a major component of basement membranes. Biopsy specimens from 56 patients with primary melanoma and 7 with cutaneous or nodal metastases were studied by immunohistochemistry. Of 39 patients with estimated good prognosis, 70.5% of melanomas were negative for MMP-2, compared with only 47% of 17 melanomas in patients who developed metastasis during the 3-year follow-up. All skin and nodal metastases were negative for MMP-2 and positive for MMP-9. Of 14 thick melanomas, 9 were mostly positive for MMP-2 expression, suggesting a possible association with the invasiveness of the melanoma. MMP-2 and MMP-9 plasma levels were analysed in another 29 patients with melanoma (10 stage I and II, 9 stage III, and 10 stage IV) and in 10 healthy controls. No difference in MMP-9 plasma levels was found among the groups. Higher MMP-2 concentrations were observed in patients with metastatic disease (stage IV) than in those with primary melanoma (stage I) or in controls. Serial levels in two patients who passed from stage I to stage III or IV showed no significant difference in MMP-2 or -9 values. We conclude that MMP-2 expression might be associated with progression of the melanoma. Circulating MMP-2 and -9 levels have shown low sensitivity and specificity, so they do not seem to be good tumour markers in patients with melanoma.
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 143 (2000), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Cidofovir [(S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl) cytosine] is a commercially available nucleotide analogue that has antiviral activity against a broad range of DNA viruses and is effective against human cytomegalovirus infection. Objectives We aimed to study the effect of cidofovir on growth of the highly aggressive melanoma tumour arising from mouse melanoma B16 cells grafted subcutaneously in C57B16/J mice. Methods Mice were treated daily with systemic cidofovir at several doses. In treated and control groups, tumour growth was measured using a calliper, and histological studies were performed. Results In untreated mice, massive invasive melanoma tumours were observed on day 5 after tumour cell grafting. Cidofovir treatment gave a dose-dependent reduction in tumour size. Tumour growth was inhibited by 62% at a dose of 37·5 mg kg−1 three times weekly, as compared with control mice treated with saline alone. At 67 mg kg−1 three times weekly, tumour growth was inhibited by 90%. Increasing the cidofovir dose to 50 or 100 mg kg−1 daily resulted in a gradual increase in the antitumoral effect of the compound. In one experiment, cidofovir was administered at 100 mg kg−1 five times weekly from the eighth day after the injection of tumour cells, when the tumour already had a volume of approximately 100 mm3. In the treatment group, on the 14th day the tumour volume was approximately 200 mm3, while in the control group it had increased to 750 mm3. Conclusions Although the mechanism is unknown, an antitumoral or antiangiogenic effect may be the reason for the activity of cidofovir in this model. In view of our findings, use of cidofovir should be further explored in the treatment of neoplastic diseases.
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of the European Academy of Dermatology and Venereology 15 (2001), S. 0 
    ISSN: 1468-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Cutaneous endosalpingiosis is a very rare entity, and to our knowledge umbilical location has been reported in only one patient who developed salpingectomy shortly after. We report cutaneous umbilical endosalpingiosis associated with severe abdominal pain that disappeared after surgical treatment.
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of dermatology 31 (1992), S. 0 
    ISSN: 1365-4632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental dermatology 17 (1992), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We report the case of a 61–year-old male who presented with a febrile illness accompanied by arthralgia and myalgia. Two months later he developed multiple subcutaneous nodules and enlarged parotid glands. Later two erythematous plaques, clinically compatible with erythema nodosum (EN), were observed. Laboratory investigations revealed abnormal levels of angiotensin converting enzyme and chest radiography showed bilateral hilar enlargement. The biopsy of the cutaneous lesions demonstrated multiple non-causeating granulomas in the subcutaneous tissue without any alterations in the epidermis and the dermis. The cultures for Mycobacteria and fungi were both negative. The clinical picture and histopathological findings were compatible with subcutaneous nodular sarcoidosis. The response to steroid treatment was satisfactory.
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental dermatology 20 (1995), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We report two patients initially diagnosed as having steatocystoma multiplex (SM), Other cysts showed characteristics of eruptive vellus hair cyst (EVHC). More than 30 and 14 cysts, respectively, were removed with histological hybrid characteristics of SM and EVHC. This suggests that SM and EVCH are two closely related entities, which represent a naevoid malformation in the area where the sebaceous duct and hair follicle meet.
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental dermatology 20 (1995), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We report a patient initially diagnosed as having toxic epidermal necrolysis, in whom later clinical and immunopathological features suggested progression to bullous pemphigoid.
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...