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J Biol Chem. 2003 Jan 24;278(4):2309-16. Epub 2002 Nov 12.
Repression of 92-kDa type IV collagenase expression by MTA1 is mediated through direct interactions with the promoter via a mechanism, which is both dependent on and independent of histone deacetylation.
Yan C, Wang H, Toh Y, Boyd DD.
Department of Cancer Biology, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Although the expression of the metastases-associated gene MTA1 correlates with tumor metastases, its role in regulating type IV collagenase expression is unknown. Enforced MTA1 expression in HT1080 cells reduced basal and 12-myristate 13-acetate-induced 92-kDa type IV collagenase (MMP-9) protein/mRNA levels. DNase I hypersensitivity and PstI accessibility assays revealed multiple regions of the MMP-9 promoter (-650/-450 and -120/+1), showing reduced hypersensitivity in the MTA1-expressing cells. Chromatin immunoprecipitation assays demonstrated MTA1 binding to the distal region, which spans several regulatory cis elements. Co-immunoprecipitation and chromatin immunoprecipitation assay experiments revealed histone deacetylase 2 (HDAC2)-MTA1 protein-protein interactions and the MTA1-dependent recruitment of HDAC2 to the distal MMP-9 promoter region, yielding diminished histone H3/H4 acetylation. However, HDAC2 binding and H3/H4 acetylation at the proximal MMP-9 region were unaffected by MTA1 expression. Furthermore, trichostatin treatment only partially relieved MTA1-repressed MMP-9 expression, indicating a HDAC-insensitive component possibly involv ing the nucleosome-remodeling Mi2 activity, which was recruited to the promoter by MTA1. In summary, (a) MMP-9 adds to a short list of MTA1-regulated genes, which so far only includes c-myc and pS2, and (b) MTA1 binds to the MMP-9 promoter, thereby repressing expression of this type IV collagenase via histone-dependent and independent mechanisms.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12431981&dopt=Abstract
Endocr J. 2000 Jun;47(3):257-60.
A struma ovarii with increased serum basement membrane components: a case report.
Iwahashi M, Nakano R.
Department of Obstetrics and Gynecology, Wakayama Medical College, Japan.
We report a case of struma ovarii with hyperthyroidism and elevated serum concentrations of type IV collagen and laminin. Circulating levels of type IV collagen and laminin were measured using specific radioimmunoassays (RIAs) for 7S collagen and the P-1 fragment of laminin, and the basement membrane components in the tumor were investigated by immunohistochemical analysis. Strong immunohistochemical staining specific for type IV collagen and for laminin was observed to be localized in the follicular walls. The serum levels of these antigens, as determined by RIA, were very high before removal of the tumor but decreased rapidly postoperatively. The present findings suggest that struma ovarii produces large amounts of type IV collagen and laminin. In addition, elevated levels of thyroid hormones might enhance the turnover of the basement membrane in various tissues.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11036868&dopt=Abstract
Minerva Med. 2000 Mar-Apr;91(3-4):59-68.
[Biochemical markers of bone turnover and YKL 40 in ankylosing spondylitis. Relation to disease activity]
[Article in Italian]
D'Amore M, Germinario G, D'Amore S, Scagliusi P.
Dipartimento di Medicina Interna e di Medicina Pubblica, Universita degli Studi, Bari.
BACKGROUND: YKL-40 is a glycoprotein produced by chondrocytes and synovial cells. The plasmatic levels of this metabolite increase in some pathologies such as rheumatoid arthritis and osteoarthrosis, so much so that it can be considered an effective marker of disease activity and in the therapeutic monitoring of these diseases. It has been interesting to dose a group of both male and female subjects affected by seronegative spondylarthritis, comparing this parameter with the disease activity indexes and with the bone turnover markers. METHODS: The study has been carried out on 48 subjects (26 males and 22 females) between 17 and 68 years affected by spondylarthritis, diagnosed in conformity with ARA standards. None of the patients carried out basic treatment or by glycocorticoids, and 22 patients took FANS when required. In these subjects the disease activity markers (VES, PCR, fibrinogen, mucoprotein) and some of the classic bone remodelling markers (blood calcium and phosphates, calciuria, phosphaturia, Ca++, Ntx, osteocalcine, bone isoenzyme of alkaline phosphatase, hydroxyproline, procollagen and YKL-40) were dosed. RESULTS: The comparison between different parameters pointed out that the highest values are obtained in subjects of most advanced age with the highest phlogosis indexes, without any correlation with sex. The quite interesting comparison shows a correlation between the bone remodelling indexes and YKL-40, being particularly remarkable when the disease is more aggressive or during relapse. CONCLUSIONS: It is then possible to confirm that, though preliminary, these data may suggest evaluations on wider case histories to research YKL-40 as a surgical monitoring marker in seronegative poliarthritis.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11037631&dopt=Abstract
Arch Esp Urol. 2000 Sep;53(7):665-71.
Intralesional recombinant interferon alpha-2b in Peyronie's disease.
Astorga R, Cantero O, Contreras D, del Rio-Martin A, Labarta-Beceiro V, Gutierrez-Elvirez A, Lima-Lopez MA, Lopez-Saura P.
General Calixto Garcia Hospital, Havana, Cuba.
OBJECTIVE: To evaluate interferon alpha-2b (IFN) in the treatment of Peyronie's disease (PD) since IFN exerts antifibrotic action through collagen synthesis inhibition and fibrolysis stimulation. METHODS: The study comprised 34 patients, aged 31 to 63, with clinical and ultrasonographic (US) diagnosis of PD, who gave their consent to enter the study. They had the disease for 10.1 +/- 5.6 (2-22) months. Ten million IU of IFN were injected intralesionally, twice weekly for 14 weeks or less if there was complete remission. Clinical evaluation included penis angle at erection, sexual dysfunction (pain, possibility of intercourse) and palpable plaque. Plaque size was evaluated by US. Systemic and local adverse reactions, and anti-IFN antibodies were monitored as well. RESULTS: Sexual dysfunction disappeared in 19/24 (79.2%) patients with this disorder, palpable lesions in 21/34 (62%), angle at erection in 15/32 (47%), and pain in 16/17 (94%). Complete clinical response was achieved in 16/34 patients (47%). Ultrasonographic response rate was 88%, (53% complete). Plaque size decreased from 56.7 +/- 42.9 (median: 35.4) before treatment to 12.7 +/- 22.6 mm2 (median: 0) (p < 0.00001; Wilcoxon's paired test). Clinical and US responses correlated. No patient showed progression. Eight of 9 patients in whom other treatments had failed responded to IFN therapy (5 complete). The main systemic adverse reaction in most patients (mild or moderate) was the flu-like syndrome expected for IFN. Local reactions, more related to the administration procedure than to IFN itself, were small hematoma (10 patients), edema (3), cysts that were excised surgically (2), and venous leak (1). No patient developed anti-IFN antibodies. CONCLUSIONS: IFN treatment can be a suitable option for the management of PD. The results appear to be better than those achieved with other procedures. Further work should include comparative studies, long-term follow-up of treated patients, and alternative ways of administration.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11037665&dopt=Abstract
Vasa. 2000 Aug;29(3):173-7.
Changes in the extracellular matrix of the vein wall--the cause of primary varicosis?
Kirsch D, Dienes HP, Kuchle R, Duschner H, Wahl W, Bottger T, Junginger T.
Department of General and Abdominal Surgery, Johannes Gutenberg-University Hospital, Mainz, Germany. Kirscch.klinik.uni-mainz.de
BACKGROUND: Conflicting theories on the development of primary varicosis have led to the molecular biological investigation of the vein wall or, more accurately, of the extracellular matrix. It was the aim of this study to quantify matrix expression and to compare pathological changes in the vein wall with valve-orientated staging of varicosis, in order to determine indicators of the primary cause of varicosis. MATERIALS AND METHODS: Three hundred seventy-two tissue specimens of greater saphenous veins were obtained from 17 patients with varicosities and categorised according to Hach stage and procurement site. The specimens were compared with 36 specimens collected from six patients without varicosities, incubated with fluorescence-stained antibodies for collagen 4, laminin, fibronectin and tenascin prior to being assessed with confocal laser scan microscopy. In addition, 22 vein specimens (16 varicose, 6 normal veins) serving as negative controls were investigated. RESULTS: Image analysis and statistical evaluation showed that compared with normal veins, varicose veins are associated with a significant increase in matrix protein expression for collagen 4, laminin and tenascin. A trend towards an increase in matrix expression was further observed for fibronectin. There was, however, no difference between varicose veins and clinically healthy vein segments inferior to a varicose segment. CONCLUSION: If the findings of the present investigation can be confirmed by other studies, alterations in the vein wall may be regarded as the primary cause of varicosis and valvular insufficiency as the result of these changes.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11037714&dopt=Abstract
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