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J Ara

Publications and source records attributed to J Ara.

At least 19 recordsLinked to original sources
PubMed2005

Schwann cell-autonomous role of neuropilin-2.

Neuropilins and group A plexins are components of receptor complexes for class 3 semaphorins, gradients of which help to guide migration of neural progenitor cells and axonal growth cones during development. We demonstrated previously that neuropilins and class 3 semaphorins are induced in sciatic nerve by crush or transection. We now report that in cultured rat Schwann cells, expression of mRNA encoding neuropilin-2 (NRP2) and plexin-A3 (PlexA3), proteins involved in semaphorin-3F (Sema3F) signal transduction, is diminished markedly by forskolin, an adenylate cyclase activator that, like axonal contact, induces Schwann cell synthesis of myelin lipids and proteins. Interestingly, Schwann cell expression of mRNA encoding NRP1, which participates in Sema3A signaling, is not downregulated by forskolin. Antibodies that recognize ectodomains of NRP2 but not control antibodies prevented cultured Schwann cells from aligning in parallel and forming columns. These results are consistent with the view that in nerves undergoing Wallerian degeneration, Schwann cell NRP2 facilitates assembly of Schwann cells into the tubular aggregates (bands of Büngner) that guide regenerating axons.

Animals↗
PubMed2001

Circulating soluble adhesion molecules in ANCA-associated vasculitis.

BACKGROUND: To evaluate whether changes in concentrations of soluble (s) E-selectin, sP-selectin, sL-selectin, intercellular adhesion molecule 1 (sICAM-1), and vascular cell adhesion molecule 1 (sVCAM-1) reflect disease activity in patients with ANCA-associated vasculitis and whether serum levels of these adhesion molecules are related to the degree of renal failure in patients with chronic renal failure (CRF). SUBJECTS AND METHODS: A sandwich ELISA was used to measure these soluble adhesion molecules in (i) sera from 20 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (10 patients with Wegener's granulomatosis (WG) and 10 patients with microscopic polyangiitis (MPA)), obtained at the time of diagnosis and during the remission period; (ii) sera from 40 patients with CRF not undergoing haemodialysis. RESULTS: At the time of diagnosis, serum levels of sE-selectin, sICAM-1 and sVCAM-1 (88+/-42 ng/ml, 437+/-184 ng/ml, 1720+/-1174 ng/ml respectively) were significantly higher in patients with ANCA-associated vasculitis than in healthy controls (P<0.0001, P=0.002 and P=0.001 respectively). Serum sP-selectin values did not differ from those obtained in normal donors. In contrast, sL-selectin levels (940+/-349 ng/ml) were significantly lower in patients than those recorded in healthy controls (P<0.0001). A significant decrease in concentrations of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 was observed between active and remission phases (P<0.0001, P=0.002, P=0.001 and P=0.001 respectively). No significant differences were observed in sL-selectin levels between active and remission phases. sL-selectin concentrations (802+/-306 ng/ml) during the remission phase remained lower than those observed in healthy controls (P<0.0001). No correlation was observed between serum creatinine and sE-selectin, sP-selectin, sICAM-1 and sVCAM-1 in patients of the CRF group. A slight negative correlation was established between creatinine and sL-selectin concentration. CONCLUSIONS: Increased serum levels of sE-selectin, sICAM-1, and sVCAM-1 and decreased levels of sL-selectin in active ANCA-associated vasculitis, and the normalization of sE-selectin, sICAM-1, and sVCAM-1 during the remission phase suggest that the concentration of soluble levels of these adhesion molecules reflects disease activity. The decrease in sP-selectin levels between active and inactive phases also suggest that this receptor may reflect clinical activity. The lack of correlation between serum levels of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 and the degree of renal failure in patients with CRF suggests that the mechanism of clearance of these molecules is not renal.

Adult↗
PubMed2001

Comparison of anti-PR3 capture and anti-PR3 direct ELISA for detection of antineutrophil cytoplasmic antibodies (ANCA) in long-term clinical follow-up of PR3-ANCA-associated vasculitis patients.

A total of 118 sera from 11 patients with anti-neutrophil cytoplasmic antibodies against proteinase-3- (PR3-ANCA) associated vasculitis were retrospectively screened by anti-PR3 capture and anti-PR3 direct ELISA tests. We studied the relationship between capture and direct ELISA scores and the clinical activity of PR3-ANCA-associated vasculitis patients during follow-up. We also studied the ability of the anti-PR3 capture ELISA to detect positive values of PR3-ANCA in clinical vasculitis relapses. Only capture ELISA presented a significant relationship (p < 0.05) with clinical activity of PR3-ANCA-associated vasculitis patients over time. Capture ELISA appears to be a reliable method for detecting clinical relapses in this group of patients. Our results indicate that the new capture ELISA test is more effective than direct ELISA in the follow-up of patients with PR3-ANCA-associated vasculitis and in the detection of relapses.

Adult↗
PubMed2000

Proteolytic degradation of tyrosine nitrated proteins.

Tyrosine nitration is a covalent posttranslational protein modification that has been detected under several pathological conditions. This study reports that nitrated proteins are degraded by chymotrypsin and that protein nitration enhances susceptibility to degradation by the proteasome. Chymotrypsin cleaved the peptide bond between nitrated-tyrosine 108 and serine 109 in bovine Cu,Zn superoxide dismutase. However, the rate of chymotryptic cleavage of nitrated peptides was considerably slower than control. In contrast, nitrated bovine Cu,Zn superoxide dismutase was degraded at a rate 1. 8-fold faster than that of control by a gradient-purified 20S/26S proteasome fraction from bovine retina. Exposure of PC12 cells to a nitrating agent resulted in the nitration of tyrosine hydroxylase and a 58 +/- 12.5% decline in the steady-state levels of the protein 4 h after nitration. The steady-state levels of tyrosine hydroxylase were restored by selective inhibition of the proteasome activity with lactacystin. These data indicate that nitration of tyrosine residue(s) in proteins is sufficient to induce an accelerated degradation of the modified proteins by the proteasome and that the proteasome may be critical for the removal of nitrated proteins in vivo.

Animals↗
PubMed2000

Caulerpin.

The crystal structure of caulerpin (dimethyl 6,13-dihydrodibenzo[b,i]phenazine-5,12-dicarboxylate, C(24)H(18)N(2)O(4)), an indole alkaloid, reported in space group Cc with an acute beta angle, has been redetermined in the correct space group, C2/c. The molecule has twofold crystallographic symmetry and is composed of two essentially planar indole groups fused to an eight-membered cyclooctatetraene ring which adopts a boat conformation. The molecular dimensions are normal. The structure is stabilized by intermolecular and intramolecular interactions involving the indole N-H atom and carbonyl O atom [N.O 3.211 (4) and 2.836 (4) A].

Journal Article↗
PubMed1999

Cytotoxic activity of marine macro-algae on Artemia salina (brine shrimp).

A total of 22 ethanol extracts of seaweed species (13 brown, 6 green and 3 red) collected from the Karachi coast were investigated for brine shrimp cytotoxicity. Of all the species, only six namely Stoechospermum marginatum, Sargassum swartzii, S. binderi, Spatoglossum asperum, Stokeyia indica (brown) and Caulerpa racemosa (green) showed significant activity. n-Hexane-soluble fractions of the ethanol extract of S. marginatum and S. swartzii were found to be responsible for the activity, whereas the methanol-soluble fractions of S. asperum and S. binderi were most active. The water extract of S. indica and C. racemosa exhibited the most prominent activity (LC50 value below 70 micrograms/mL) when compared with the ethanol extracts and their fractions. Cytotoxic activity may be due to the compounds differing in polarity.

Animals↗
PubMed1999

Relationship between ANCA and disease activity in small vessel vasculitis patients with anti-MPO ANCA.

BACKGROUND: We analysed the usefulness of antineutrophil cytoplasmic antibodies (ANCA) as a marker of clinical activity in patients with small vessel vasculitis associated with anti-myeloperoxidase (MPO) ANCA. METHODS: We studied a group of 25 patients, 15 with microscopic polyangitis and 10 with renal limited vasculitis, so-called rapidly progressive glomerulonephritis type III. The clinical and serological follow-up was accomplished quarterly over an average of 2.79 +/- 2.08 years (range 0.25-6 years). ANCA was analysed by indirect immunofluorescence and enzyme-linked immunosorbent assays (ELISAs). RESULTS: At the time of diagnosis, all patients were ANCA positive (P-ANCA and anti-MPO). Following a standardized treatment, all patients except one achieved complete remission of vasculitis in <3 months. One patient suddenly died during the active phase (1 month of follow-up) and with positive ANCA. Seroconversion from positive to negative occurred in 24/25 patients (96%). Eighteen of these 24 patients (75%) achieved the seroconversion within the first 6 months. During the follow-up, two patients had four major relapses, all of them associated with positive ANCA. ANCA seroconversion from negative to positive was observed in one patient with microscopic polyangitis without clinical relapse of vasculitis. CONCLUSION: ANCA should be used in conjunction with other markers of disease activity in the management of microscopic polyangitis and renal limited vasculitis patients with anti-MPO ANCA.

Adult↗
PubMed1998

[Usefulness of anti-neutrophil cytoplasmic antibodies, anti-proteinase 3 and anti-myeloperoxidase in management of small vessel vasculitis].

BACKGROUND: Analysis of usefulness of antineutrophil cytoplasmic antibodies (AN-CA) as a marker of clinical activity in small vessel vasculitis. PATIENTS AND METHODS: 33 patients, 10 patients with Wegener's granulomatosis (WG) and 23 with microscopic polyangiitis (MPA) and rapidly progressive glomerulonephritis type III (RPGN III). The clinic and serologic follow-up was accomplished every 3 months during an average of 19 (SD, 24) months (range 3-52 months. The serologic follow-up included the determination of ANCA by indirect immunofluorescence (IFI) and ELISA, as well as the serum level of C reactive protein (RCP). RESULTS: At the time of diagnosis all patients were ANCA positive by IFI and ELISA. The seroconversion of ANCA from positive to negative was produced in 30/33 patients (90%). Twenty-six out of these 30 patients (87%) achieved the seroconversion within the first 6 months. During the follow-up 4 patients had a major relapse, all with positive ANCA. In 2 patients, one of each group, seroconversion from negative to positive was not associated with clinical relapse of vasculitis. CONCLUSION: ANCA should be used in conjunction with other indices of disease activity in patients with small vessel vasculitis.

Adult↗
PubMed1998

Inactivation of tyrosine hydroxylase by nitration following exposure to peroxynitrite and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

The decrement in dopamine levels exceeds the loss of dopaminergic neurons in Parkinson's disease (PD) patients and experimental models of PD. This discrepancy is poorly understood and may represent an important event in the pathogenesis of PD. Herein, we report that the rate-limiting enzyme in dopamine synthesis, tyrosine hydroxylase (TH), is a selective target for nitration following exposure of PC12 cells to either peroxynitrite or 1-methyl-4-phenylpyridiniun ion (MPP+). Nitration of TH also occurs in mouse striatum after MPTP administration. Nitration of tyrosine residues in TH results in loss of enzymatic activity. In the mouse striatum, tyrosine nitration-mediated loss in TH activity parallels the decline in dopamine levels whereas the levels of TH protein remain unchanged for the first 6 hr post MPTP injection. Striatal TH was not nitrated in mice overexpressing copper/zinc superoxide dismutase after MPTP administration, supporting a critical role for superoxide in TH tyrosine nitration. These results indicate that tyrosine nitration-induced TH inactivation and consequently dopamine synthesis failure, represents an early and thus far unidentified biochemical event in MPTP neurotoxic process. The resemblance of the MPTP model with PD suggests that a similar phenomenon may occur in PD, influencing the severity of parkisonian symptoms.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

Hypertrophic cardiomyopathy and systemic lupus erythematosus.

We report the case of a 45 year-old woman with systemic lupus erythematosus (SLE), who developed clinical and echocardiographic signs of hypertrophic cardiomyopathy. Neither a family history of cardiomyopathy or sudden death nor a personal history of hypertension or valvular lesions were present. The association of SLE with hypertrophic cardiomyopathy has been previously described in only 2 patients.

Cardiomyopathy, Hypertrophic↗
PubMed1995

Dot-ELISA for the rapid detection of gentamicin in milk.

A dipstick dot-ELISA for the detection of gentamicin in milk of dairy cattle is reported for the first time. The test is based on a sandwich ELISA using high affinity monoclonal antibodies to gentamicin. Antibodies were adsorbed to nitrocellulose filters, blocked, dried, and stored for several weeks before use. The dipstick ELISA detected gentamicin at a concentration of 0.1 microgram/ml and produced strongly positive results at 0.2 microgram-0.3 microgram/ml. This ELISA is highly specific and no false positives were detected when tested against various aminoglycoside analogs including streptomycin, kanamycin, bekanamycin, amikacin, neomycin, and tobramycin. Further, the elimination in cow milk of gentamicin residues following intramammary administration of the drug was studied in two dairy cattle using dot-ELISA. Milk gentamicin levels were detected at post injection hours up to 120 hr in each of the two dairy cattle. It therefore, appears that gentamicin residues can still be detected in milk after 5 days using dot-ELISA. Based on the simplicity of performance and the economical nature of the test system, dipstick is recommended as a suitable method for wide scale use in field studies and diagnostic laboratories.

Animals↗
PubMed1995

Pakistan national diabetes survey: prevalence of glucose intolerance and associated factors in Shikarpur, Sindh Province.

The prevalence of diabetes mellitus and impaired glucose tolerance (IGT) and their relationship to age and obesity was estimated in the rural town of Shikarpur in Sindh Province, Pakistan by a population-based survey in 1994. Oral glucose tolerance tests were performed in a stratified random sample of 967 adults (387 men, 580 women) aged 25 years and above. The diagnoses of diabetes and IGT were made on the basis of WHO criteria. The response rate was 71% for men and 80% for women. The prevalence of diabetes was 16.2% (9.0% known, 7.2% newly diagnosed) in men, and 11.7% (6.3% known, 5.3% newly diagnosed) in women. The prevalence rose with age to a peak of 30% and 21% in 65-74 year-old men and women respectively. IGT was detected in 8.2% of men and 14.3% of women. Thus, total glucose intolerance (diabetes and IGT combined) was present in 25% of subjects examined. These results indicate that glucose intolerance in South Asians can no longer be regarded as a problem confined to migrant communities. Of the 72 subjects previously known to have diabetes, none was using insulin treatment, but 57 (79%) took oral hypoglycaemic agents. Central obesity and positive family history were strongly associated with diabetes, as was prevalence of hypertension. The association with central obesity was greater for women than for men, and suggests important, modifiable risk factor(s) related to lifestyle.

Adult↗
PubMed1995

Antigenic specificity of anti-ROS DNA antibodies: involvement of lysyl residues in antigen binding.

The antigenicity of native DNA modified with reactive oxygen species was examined. Goats were immunized with the modified polymer and the antibody response was estimated by direct binding and competition ELISA. The induced antibodies bound ROS-DNA and showed considerable binding to native DNA as well. Specificity analysis of the purified antibodies revealed the recognition of native B-, A- and allied conformations presented by various synthetic polynucleotides. The contribution of lysine residues to the immunochemical binding of purified IgG was investigated by modifying the free amino groups of lysine residues. The modification of lysine residues paralleled loss in IgG binding to ROS-DNA to the extent of 50%, suggesting that such residues might be involved in the antigen binding site of immunoglobulin molecule.

Acylation↗