Coordinate enhancement of gelatinase a mRNA and activity levels in human fibroblasts in response to breast-adenocarcinoma cells

Gelatinases/type-IV collagenases are metalloproteinases involved in some carcinoma invasion and metastatic processes. The exact cellular source of the 72-kDa gelatinase A is controversial. We have analyzed the expression of mRNA coding for gelatinase A in vivo by in situ hybridization on breast-cancer tissues. The mRNA for gelatinase A was present in fibroblasts. We have therefore evaluated the gelatinase-A activity in vitro, in co-cultures of different breast adenocarcinoma cell lines and human fibroblasts. In monoculture, none of the tumor cells tested produced detectable amounts of gelatinase A. The gelatinase-A activity was enhanced in cultures of fibroblasts maintained in the presence of MDA-MB 231 or SKBR3 cells, or their conditioned medium. This increased enzymatic activity was evidenced both in the culture medium and in the membrane fraction and was paralleled by enhancement of the steady-state levels of mRNA. These results are an in vitro demonstration of a regulation of fibroblasts gelatinase-A production by soluble factors secreted by breast-tumor cells.     

Characteristic ocular findings in Asian children with Down syndrome

AIMS/PURPOSE: To identify the characteristic ocular findings in Asian children with Down syndrome. METHODS: A total of 123 Korean children with Down's syndrome between 6 months and 14 years of age were examined for ocular findings from March 1999 to April 2000. Ocular examinations including visual acuity assessment, slit-lamp biomicroscopy, ocular motility, cycloplegic refraction, and ophthalmoscopy were performed. RESULTS: The ocular findings in decreasing prevalence were the following: upward slanting of the palpebral fissure (78 patients, 63%), epicanthus (75 patients, 61%), epiblepharon (66 patients, 54%), astigmatism (38 patients, 31%), hyperopia (35 patients, 28%), myopia (31 patients, 25%), strabismus (31 patients, 25%, 18 esotropia and 13 exotropia), nystagmus (27 patients, 22%), nasolacrimal duct obstruction (21 patients, 17%), blepharoconjunctivitis (20 patients, 16%), retinal abnormalities (18 patients, 15%), cataract (four patients, 13%), and glaucoma (one patient, 0.8%). Brushfield spots and keratoconus were not found. CONCLUSIONS: Asian children with Down syndrome demonstrate unreported, high incidence of epiblepharon, the high rate of exotropia, and essentially no notable Brushfield spots, which are in contrast to the ocular findings in Caucasian patients with Down syndrome.     

Matrix and serine protease expression during leukemic cell differentiation induced by aclacinomycin and all-trans-retinoic acid

In myeloid leukemia, immature leukemic cells are able to egress into peripheral blood to infiltrate extra-medullary organs. We therefore analyzed the migrating and invasive potential of human HL-60 and NB4 cell lines, representative of acute myelogenous leukemia, their ability to express matrix metalloproteases (MMPs), tissue inhibitors of metalloproteases (TIMPs) and urokinase plasminogen activator (uPA) in response to differentiating agents. Granulocytic differentiation by all-trans-retinoic acid (ATRA) and aclacinomycin (ACLA) strongly increased HL-60 and NB4 cell migration and invasion. At mRNA and protein levels, these cell lines produced significant amounts of MMP-9 (HL-60相似文献   

Determination of codeine in urine and drug formulations using a clay-modified screen-printed carbon electrode

Both flow-injection analysis and square-wave stripping voltammetry were evaluated for the determination of codeine in pharmaceutical formulations using a nontronite clay-modified screen-printed carbon electrode. Compared with a bare screen-printed carbon electrode, the nontronite clay-modified screen-printed carbon electrode exhibited a marked enhancement of the current response of codeine. A linear calibration plot was obtained over the 2.5-45 microM range (correlation coefficient=0.999) in pH 6.0 phosphate buffer solution with a detection limit of 20 nM (S/N=3) by square-wave voltammetry (SWV). While, in flow-injection analysis, the linearity was over 5-120 ng range with a detection limit of 1 ng in 20 microl loop. The nontronite clay-modified screen-printed carbon electrode can be either disposable or reused since the renewal gave a good reproducible surface. Quantitative analysis was performed by the standard addition method for codeine content in both urine and commercially available drugs.     

Prenatal exposure to influenza as a risk factor for adult schizophrenia

OBJECTIVE: Several, but not all epidemiological studies, have demonstrated a positive correlation between exposure to the virus during the second trimester of pregnancy and an increased risk to the infants for subsequently developing schizophrenia. The present study is the first be designed in France to examine the risk of gestational exposure to the influenza virus and subsequent development of schizophrenia. METHOD: A total of 974 adults with schizophrenia born between 1949 and 1981 were compared for risk of exposure to influenza with their non-schizophrenic siblings and with matched control patients. RESULTS: Significantly more schizophrenic subjects than controls (both groups) had been exposed to the influenza virus during the fifth month of pregnancy (OR=2.24, CI: 1.49-3.35, and OR=1.61, CI: 1.04-2.49). CONCLUSION: These results suggest that influenza infection during pregnancy is a neurodevelopmental risk factor for schizophrenia in adult life.     

Clinical and molecular analysis of chinese patients with thyrotoxic periodic paralysis

Although sporadic thyrotoxic periodic paralysis (TPP) has a much higher prevalence in Asian than in all the other populations studied so far, it is also increasingly being seen at the emergency departments of the West, hence, it is vital to stress the importance of recognizing it. TPP shares some similarities with hypokalemic periodic paralysis (HOKPP). However, the pathophysiology of TPP and the reasons for this higher incidence are not known. We hypothesized that some mutations in the CACNA1S gene, which has been implicated in familial HOKPP, might play a role in TPP. We present 5 Chinese patients who suffer from TPP and demonstrate typical clinical features. No mutation was found on the whole CACNA1S gene. Therefore other molecular mechanisms will have to be examined in order to explain the different TPP incidences.     

Serum IgG antibodies to P0 dimer and 35 kDa P0 related protein in neuropathy associated with monoclonal gammopathy

BACKGROUND: Peripheral neuropathies (PN) associated with monoclonal gammopathy (MG) are widely considered as autoimmune disorders, but the putative role of incriminated antigens is still not understood. OBJECTIVE: Fifty five patients with PN associated with MG were studied to investigate whether new antigens could be found, and to evaluate their relation to clinical manifestations. METHODS: An immunological study was conducted on patient sera to identify autoreactivities against nerve proteins by western blotting. Antigen proteins were purified and analysed by proteomic tools. Correlation with ultrastrucural and clinical features was then studied. RESULTS: Of the 55 patients suffering from PN associated with MG, 17 exhibited IgG autoantibodies directed against peripheral nerve proteins of 35, 58, and 60 kDa. N-terminal microsequencing and mass spectrometry analyses of the 35 kDa protein revealed perfect peptidic matching with 47% of the amino acid sequence of P0, whereas the 58 and 60 kDa proteins were identified as the reduced and non-reduced forms of a P0 dimer. Deglycosylation did not affect IgG binding to the 35 kDa P0 related protein, suggesting a peptidic epitope. In contrast, deglycosylation abolished IgG recognition of the P0 dimer protein, so that a carbohydrate moiety may be implicated in the epitope formation. This confirmed the existence of two different types of IgG, one recognising the 58 and 60 kDa proteins and one directed against the 35 kDa protein. CONCLUSIONS: This is the first report of antibody activity directed against the dimeric association of P0. Although P0 oligomerisation and adhesion properties play a crucial part in the myelin sheath compaction, the pathogenic significance of these autoantibodies needs further investigations to be elucidated.     

Lyme borreliosis

Lyme disease is a multisystemic disease caused by a spirochete, Borrelia Burgdorferi that is transmitted by ticks. A clinical diagnosis is easy when a tick bite is followed 3 weeks later by erythema migrans, than by involvement of nervous system, joints or heart. In case of neuroborreliosis, serological tests, performed in blood and cerebro-spinal fluid, support the diagnosis and patients recover rapidly with antibacterial treatments. However an accurate diagnosis remains sometimes problematic, especially distinction between a coincidental positive serologic test and a nervous system Lyme borreliosis which require antibiotics. Furthermore, the role of autoimmunity in the pathophysiology of late Lyme disease, antibiotic choice in early disease, duration of treatment, and utility of vaccination are discussed.     

Radiation-induced aneurysm of the cavernous internal carotid artery

We report a case of intra-cranial aneurysm of the left cavernous internal carotid artery occurring 27 years after radiotherapy of the pterygopalatine fossa for Hodgkin disease. The development of the aneurysm within the irradiation field, the long latency after radiotherapy, the normality of carotid angiography before radiotherapy and the absence of other etiologies led to the diagnosis of radiation-induced aneurysm. The main characteristics of radiation-induced intra-cranial aneurysms are reviewed.