Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
Add more filters










Database
Publication year range
1.
Exp Dermatol ; 19(7): 654-60, 2010 Jul 01.
Article in English | MEDLINE | ID: mdl-20456494

ABSTRACT

Stat3 is activated by the outer stressors, such as ultraviolet (UV) exposure. In this study, we investigated the Stat3 response to UV irradiation in human epidermal keratinocytes and dermal fibroblasts. Results indicated that UVB and UVC differentially activate Stat3 in these cells. The UV-induced Stat3 activation was mediated by both reactive oxygen species (ROS) and DNA damage, and the dominancy of ROS and DNA damage to activate Stat3 depended on the wavelength of UV. By using fibroblasts from a patient with xeroderma pigmentosum A (XP-A) and those transfected with human XPA gene, we found that UVB activates Stat3 via both ROS and DNA damage, while UVC does so mainly via DNA damage. The present data suggest that Stat3 activation in UV-exposed human skin is one of the initial events where DNA damage and ROS are involved.


Subject(s)
DNA Damage , Fibroblasts/metabolism , Fibroblasts/radiation effects , Keratinocytes/metabolism , Keratinocytes/radiation effects , STAT3 Transcription Factor/metabolism , Ultraviolet Rays/adverse effects , Binding Sites , Cells, Cultured , Humans , Phosphorylation , Reactive Oxygen Species/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , STAT3 Transcription Factor/chemistry , Serine/chemistry , Transfection , Up-Regulation/radiation effects , Xeroderma Pigmentosum/genetics , Xeroderma Pigmentosum/metabolism , Xeroderma Pigmentosum Group A Protein/genetics , Xeroderma Pigmentosum Group A Protein/metabolism
2.
Amyloid ; 17(1): 32-5, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20132088

ABSTRACT

We report here two patients with amyloidogenic transthyretin (ATTR) Val30Met familial amyloid polyneuropathy (FAP) who developed numbness in both hands and were diagnosed as having bilateral carpal tunnel syndrome (CTS). In both patients systemic TTR amyloidosis consisting of polyneuropathy affecting both upper and lower limbs and/or autonomic dysfunction gradually appeared after surgery for CTS. Although CTS associated with TTR amyloidosis has been known as an initial symptom in some patients with ATTR non-Val30Met FAP and those with senile systemic amyloidosis, this is the first report of ATTR Val30Met FAP patients starting with upper limb neuropathy including CTS-like symptoms. It is also notable that both patients had no genealogical relationship with two Japanese endemic foci of this disease.


Subject(s)
Amyloid Neuropathies, Familial/genetics , Amyloid/genetics , Carpal Tunnel Syndrome/genetics , Mutation, Missense , Prealbumin/genetics , Aged , Amino Acid Substitution , Amyloid Neuropathies, Familial/etiology , Carpal Tunnel Syndrome/etiology , Female , Humans , Japan , Male , Middle Aged
3.
J Biol Chem ; 284(44): 30416-23, 2009 Oct 30.
Article in English | MEDLINE | ID: mdl-19755418

ABSTRACT

The growth of most melanoma cells in vitro is inhibited by the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). In this study, the involvement of the signal transducer and activator of transcription 3 (STAT3) in the TPA-induced growth inhibition of melanoma cells was examined. The in vitro growth and DNA synthesis of five melanoma cell lines, whose STAT3 was activated (phosphorylated), was inhibited by TPA, whereas that of WM35 and WM39 cells, whose STAT3 activity was at negligible levels, was considerably slow and not affected by TPA. Blockade of STAT3 activity by small interfering RNAs suppressed the growth of WM1205Lu cells containing constitutively activated STAT3. Treatment of WM1205Lu cells with TPA decreased both the phosphorylated STAT3 and the DNA-binding activity of STAT3. Pretreatment of WM1205Lu cells with either a protein-tyrosine phosphatase inhibitor or a protein kinase C (PKC) inhibitor prevented the inhibitory effects of TPA on the level of phosphorylated STAT3. The five melanoma cell lines containing phosphorylated STAT3 commonly expressed PKCalpha, PKCdelta, and PKCepsilon. Introduction of the dominant negative mutant of one of these PKC isoforms into WM1205Lu cells inhibited the TPA-induced dephosphorylation of STAT3. A Src inhibitor attenuated the STAT3 phosphorylation in WM1205Lu cells. These results indicate that constitutively activated STAT3 is positively regulated by c-Src and negatively regulated by a PKC-activated tyrosine phosphatase(s) in melanoma cells. Because TPA did not affect c-Src activity, we conclude that the growth inhibitory effect of TPA on melanoma cells is mediated through inactivation of STAT3 by a PKC-activated tyrosine phosphatase(s).


Subject(s)
Cell Proliferation/drug effects , Melanoma/drug therapy , Protein Kinase C/metabolism , Protein Tyrosine Phosphatases/metabolism , STAT3 Transcription Factor/antagonists & inhibitors , Tetradecanoylphorbol Acetate/pharmacology , Antineoplastic Agents/pharmacology , CSK Tyrosine-Protein Kinase , Cell Line, Tumor , DNA/metabolism , Humans , Melanoma/pathology , Phosphorylation , Protein-Tyrosine Kinases , Proto-Oncogene Proteins , src-Family Kinases
5.
Brain Nerve ; 61(1): 77-81, 2009 Jan.
Article in Japanese | MEDLINE | ID: mdl-19177810

ABSTRACT

A 77-years-old woman was admitted to our hospital due to uncontrolled myoclonus and generalized seizure. Since the age of 17, she has been suffering from myoclonic jerks and partial convulsions in her right arm. Administration of several unknown anticonvulsants had not alleviated her condition. She was able to spend her life without a handicap, except for the symptoms described above. She has been experiencing psychological stress since the age of 50, which has resulted in worsening of her symptoms, and she was prescribed phenytoin, carbamazepine, and phenobarbital, which were also ineffective. When a generalized convulsive attack occurs, she shows rapid muscle twitches in her right arm and her consciousness is clear. She also has cerebellar ataxia in her extremities. Brain magnetic resonance imaging (MRI) showed obvious cerebellar atrophy, and an electroencephalogram revealed a diffuse spike and wave complexes. A surface electromyogram (EMG) confirmed myoclonus in both arms. We diagnosed her as having juvenile myoclonus epilepsy and initiated sodium valproate monotherapy, which relieved the symptoms. The observed cerebellar ataxia might be due to long-term administration of phenytoin. When a neurologist encounters an intractable seizure without loss of consciousness, surface EMG is useful for diagnosing this treatable disease.


Subject(s)
Diagnostic Errors , Electromyography , Epilepsies, Partial , Myoclonic Epilepsy, Juvenile/diagnosis , Myoclonic Epilepsy, Juvenile/drug therapy , Aged , Cerebellar Ataxia/chemically induced , Electroencephalography , Female , Humans , Magnetic Resonance Imaging , Phenytoin/adverse effects , Treatment Outcome , Valproic Acid/therapeutic use
6.
Rinsho Shinkeigaku ; 46(3): 227-9, 2006 Mar.
Article in Japanese | MEDLINE | ID: mdl-16642936

ABSTRACT

We report here a case of isolated hypoglossal nerve palsy probably caused by dural arteriovenous fistula (DAVF). A 51-year-old woman was admitted to our hospital complaining headache, tinnitus, and tongue atrophy. Three years before, she first experienced right-sided pulsatile headache and tinnitus which persisted until admission. One week before, she noticed her tongue deviated to right. On admission, physical and neurological examinations showed no abnormal findings except for bruits on right neck and bilateral orbital areas, and atrophy of right tongue. Brain MRI was not remarkable. MRA and conventional angiography disclosed DAVF. We conclude that differential diagnoses for isolated hypoglossal paralysis should include DAVF.


Subject(s)
Central Nervous System Vascular Malformations/complications , Hypoglossal Nerve Diseases/etiology , Central Nervous System Vascular Malformations/diagnosis , Cerebral Angiography , Female , Headache , Humans , Magnetic Resonance Angiography , Middle Aged , Tinnitus/etiology
7.
Exp Dermatol ; 15(4): 291-9, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16512876

ABSTRACT

Signal transducer and activator of transcription 3 (Stat3), a cytoplasmic transcription factor, is constitutively activated in various types of cancer. Previous investigations have demonstrated that Stat3 plays important roles in cell growth, survival, differentiation, and transformation. The constitutive activation of Stat3 in human malignancies is an important key to maintain the characteristics of a malignant tumor, such as the rate of proliferation and/or immortalization, and inhibition of Stat3 function could be a potent therapeutic approach. In order to elucidate the role of Stat3 in tumors, cutaneous squamous cell carcinoma (SCC) cells, which have constitutive activation of Stat3 in vivo and in vitro, were used for this study. To investigate the effect of specific inhibition of Stat3 in SCC cells, we developed small interfering RNAs (siRNAs) that target Stat3, and which effectively prevent its expression in vitro. Introduction of Stat3 siRNA into SCC cells led to inhibition of growth and changes in morphology but did not induce apoptosis. Stat3 siRNA-transfected SCC cells had impaired tumor growth in nude mice. These findings demonstrate that Stat3 plays a critical role in the tumorigenesis, but not in the cell survival, of SCC cells and suggest that additional pro-apoptotic signals are necessary for the induction of apoptosis.


Subject(s)
Carcinoma, Squamous Cell/pathology , Cell Proliferation , Cell Survival , STAT3 Transcription Factor/physiology , Skin Neoplasms/pathology , Animals , Apoptosis , Blotting, Western , Carcinoma, Squamous Cell/chemistry , Carcinoma, Squamous Cell/physiopathology , Cell Line, Tumor , Cyclin D1/analysis , Cyclin D1/genetics , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Mice , Mice, Nude , Proliferating Cell Nuclear Antigen/analysis , Proliferating Cell Nuclear Antigen/genetics , Proto-Oncogene Proteins c-bcl-2/analysis , Proto-Oncogene Proteins c-bcl-2/genetics , RNA, Small Interfering/pharmacology , STAT3 Transcription Factor/genetics , Skin Neoplasms/chemistry , Skin Neoplasms/physiopathology , Transfection , bcl-X Protein/analysis , bcl-X Protein/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...