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Biomedical subjects

R Grau

Publications and source records attributed to R Grau.

At least 19 recordsLinked to original sources
PubMed2002

Factors promoting colonization by legionellae in residential water distribution systems: an environmental case-control survey.

As part of a case-control study of community-acquired Legionnaires' disease, several factors related to residential water distribution systems and public drinking water systems were studied in the homes of 124 patients with community-acquired Legionnaire's disease and in the homes of 354 controls. The presence of water reservoirs and hot water tanks was studied in residential systems. Factors such as deficient chlorine levels, pipe repairs and other work, water flow interruptions, the use of alternative water sources, inadequate cleaning operations in public water reservoirs, and the position of the home within the public network (and whether this location constituted an endpoint) were studied in public water supply systems. Levels of legionellae in domestic water samples were also measured. Although the use of water reservoirs and hot water tanks promotes colonization by legionellae in residential systems, none of the variables studied seems to increase the incidence of community-acquired Legionnaires' disease.

Case-Control Studies↗
PubMed2001

Selective inhibition of vascular endothelial growth factor-mediated angiogenesis by cyclosporin A: roles of the nuclear factor of activated T cells and cyclooxygenase 2.

Cyclosporin A (CsA) is an immunosuppressive drug that inhibits the activity of transcription factors of the nuclear factor of activated T cells (NFAT) family, interfering with the induction of cytokines and other inducible genes required for the immune response. Here we show that CsA inhibits migration of primary endothelial cells and angiogenesis induced by vascular endothelial growth factor (VEGF); this effect appears to be mediated through the inhibition of cyclooxygenase (Cox)-2, the transcription of which is activated by VEGF in primary endothelial cells. Consistent with this, we show that the induction of Cox-2 gene expression by VEGF requires NFAT activation. Most important, the CsA-mediated inhibition of angiogenesis both in vitro and in vivo was comparable to the Cox-2 inhibitor NS-398, and reversed by prostaglandin E(2). Furthermore, the in vivo corneal angiogenesis induced by VEGF, but not by basic fibroblast growth factor, was selectively inhibited in mice treated with CsA systemically. These findings involve NFAT in the regulation of Cox-2 in endothelial cells, point to a role for this transcription factor in angiogenesis, and may provide a novel mechanism underlying the beneficial effects of CsA in angiogenesis-related diseases such as rheumatoid arthritis and psoriasis.

Angiogenesis Inhibitors↗
PubMed2000

Differential processing of propeptide inhibitors of Rap phosphatases in Bacillus subtilis.

In the phosphorelay signal transduction system for sporulation initiation in Bacillus subtilis, the opposing activities of histidine kinases and aspartyl phosphate phosphatases determine the cell's decision whether to continue with vegetative growth or to initiate the differentiation process. Regulated dephosphorylation of the Spo0A and Spo0F response regulators allows a variety of negative signals from physiological processes that are antithetical to sporulation to impact on the activation level of the phosphorelay. Spo0F approximately P is the known target of two related phosphatases, RapA and RapB. In addition to RapA and RapB, a third member of the Rap family of phosphatases, RapE, specifically dephosphorylated the Spo0F approximately P intermediate in response to competence development. RapE phosphatase activity was found to be controlled by a pentapeptide (SRNVT) generated from within the carboxy-terminal domain of the phrE gene product. A synthetic PhrE pentapeptide could (i) complement the sporulation deficiency caused by deregulated RapE activity of a phrE mutant and (ii) inhibit RapE-dependent dephosphorylation of Spo0F approximately P in in vitro experiments. The PhrE pentapeptide did not inhibit the phosphatase activity of RapA and RapB. These results confirm previous conclusions that the specificity for recognition of the target phosphatase is contained within the amino acid sequence of the pentapeptide inhibitor.

Amino Acid Sequence↗
PubMed1998

De novo fatty acid synthesis is required for establishment of cell type-specific gene transcription during sporulation in Bacillus subtilis.

A hallmark of sporulation of Bacillus subtilis is the formation of two distinct cells by an asymmetric septum. The developmental programme of these two cells involves the compartmentalized activities of sigmaE in the larger mother cell and of sigmaF in the smaller prespore. A potential role of de novo lipid synthesis on development was investigated by treating B. subtilis cells with cerulenin, a specific inhibitor of fatty acid biosynthesis. These experiments demonstrated that spore formation requires de novo fatty acid synthesis at the onset of sporulation. The transcription of the sporulation genes that are induced before the formation of two cell types or that are under the exclusive control of sigmaF occurred in the absence of fatty acid synthesis, as monitored by spo-lacZ fusions. However, expression of lacZ fusions to genes that required activation of sigmaE for transcription was inhibited in the absence of fatty acid synthesis. The block in sigmaE-directed gene expression in cerulenin-treated cells was caused by an inability to process pro-sigmaE to its active form. Electron microscopy revealed that these fatty acid-starved cells initiate abnormal polar septation, suggesting that de novo fatty acid synthesis may be essential to couple the activation of the mother cell transcription factors with the formation of the differentiating cells.

Bacillus subtilis↗
PubMed1998

Antiribonucleoprotein antibodies in children with HIV infection: a comparative study with childhood-onset systemic lupus erythematosus.

A number of clinical and laboratory features of HIV infection are found in systemic lupus erythematosus (SLE). The objective of this study was to analyze the presence of circulating antibodies to small nuclear ribonucleoproteins (snRNP) in both diseases. Sera from 44 HIV-infected children, from 22 patients with childhood-onset SLE, and from 50 healthy children were studied. Anti-snRNP antibodies were detected by ELISA using recombinant and affinity-purified nuclear antigens, by counterimmunoelectrophoresis (CIE), and by immunoblotting using extractable nuclear antigens. Results included the detection of anti-snRNP antibodies by ELISA in 30 HIV-infected patients (68.1%) and 19 SLE patients (86.3%). These antibodies were directed against U1-RNP (61.3% and 77.2%, respectively), Sm (29.5% and 54.5%, respectively), 60 kDa Ro/SS-A (47.7% and 50%, respectively), and La/SS-B proteins (18.1% and 9%, respectively). None of the HIV-infected children and 11 SLE patients (50%) showed anti-snRNP antibodies by CIE. None of the HIV-infected patients showed anti-70 kDa U1-RNP or anti-D-Sm antibodies by immunoblotting. No differences between the two groups were noted on the presence of nonprecipitating anti-snRNP antibodies. No such reactivities were observed among the normal sera tested. The authors concluded that nonprecipitating anti-snRNP antibodies in HIV-infected children are as frequent as in childhood-onset SLE. The significance of these antibodies is not clear at present. Although polyreactive and low-affinity antibodies and a mechanism of molecular mimicry may explain these results, a specific stimulation of B cells by nuclear antigens could not be excluded.

Adolescent↗
PubMed1998

[Prevalence and features of headache and migraine in childhood].

INTRODUCTION: A study of the prevalence of childhood cephalea has been carried on. MATERIAL AND METHODS: We studied a sample of children aged from 3 to 14 years old that consulted to different public health services clinics for control routine. We used an interview based in a questionnaire planned to be answered by parents and the child himself. RESULTS AND CONCLUSIONS: The more relevant results were: 1. Prevalence of cephalea 42%; 2. Prevalence of migraine according to Vahlquist and Kurtz criteria: 8.7% and 6.5% respectively (confidence intervals between 4.4% and 11.1%); 3. Higher proportion of girls for both cephalea and migraine; 4. Higher frequency of cephalea and the migraine type headache are facts related to the decision of seeking medical assistance; 5. 87% of children with migraine from the sample have relatives with intermittent cephalea; 6. Patients selected as having migraine, according to Vahlquist criteria, have the following predominant symptoms: Unilateral condition, vomiting/ nausea, improving with sleep, photophobia, phonophobia, changes in physical facial appearance, need to interrupt activities, pulsation quality, and visual aura.

Adolescent↗
PubMed1998

Anti-BB'-Sm antibodies, anticardiolipin antibodies, and thrombosis in systemic lupus erythematosus.

OBJECTIVE: Anticardiolipin antibodies (aCL) are associated with thrombosis in patients with systemic lupus erythematosus (SLE). Our aim was to determine whether there is an association between aCL, anti-Sm antibodies, and thrombosis in patients with SLE. METHODS: Sera from 153 patients with SLE were studied by ELISA, immunoblotting, and counter-immunoelectrophoresis (CIE) for anti-Sm antibodies, aCL and anti-dsDNA antibodies were detected by ELISA and radioimmunoassay, respectively. RESULTS: Anti-Sm antibodies were detected in 62 patients (40.5%) by ELISA and in 16 (10.4%) by CIE; IgG-anti-BB'-Sm in 44 (28.7%) by immunoblotting; IgG-aCL in 82 (53.5%), IgM-aCL in 44 (28.7%), and anti-dsDNA antibodies in 128 (83.6%). Anti-Sm and anti-dsDNA antibodies were significantly more frequent in patients with than in patients without aCL. Of the 89 patients with aCL, 36 (40.4%) showed IgG-anti-BB'-Sm antibodies (OR: 4.7; 95% CI: 2-10.5). Thrombosis was present in 20 (22.4%) SLE patients with aCL and in two (3.1 %) SLE patients without aCL (OR: 8.9; 95% CI: 2.4-31.8). Of the 22 patients with thrombosis, five (22.7%) had precipitating anti-Sm antibodies (OR: 3.2; 95% CI: 1.04-9.8) and 14 (63.6%) showed IgG-anti-BB'-Sm antibodies (OR: 5.8; 95% CI: 2.3-14). Anti-BB'-Sm and aCL were significantly more frequent in patients with anti-dsDNA antibodies (32 and 62%) than in patients without these antibodies (12 and 36%) (OR: 3.4 and 2.9; 95% CI: 1.03-11.1 and 1.2-6.7, respectively). CONCLUSION: IgG-anti-BB'-Sm antibodies are associated with aCL, anti-dsDNA, and thrombosis in patients with SLE. Our findings suggest a possible association between anti-Sm, anti-dsDNA, and aCL responses in these patients.

Adult↗
PubMed1997

A novel histidine kinase inhibitor regulating development in Bacillus subtilis.

Kinase A is the sensor histidine kinase responsible for processing postexponential phase information and providing phosphate input to the phosphorelay that activates developmental transcription via phosphorylated Spo0A. A protein inhibitor, KipI, of kinase A was discovered encoded in an operon of genes of unknown function but regulated by the availability of fixed nitrogen. KipI is a potent inhibitor of the autophosphorylation reaction of kinase A but does not inhibit phosphate transfer to the Spo0F response regulator once kinase A is phosphorylated. KipI is an inhibitor of the catalytic domain of kinase A affecting the ATP/ADP reactions and not the phosphotransferase functions of this domain. The inhibitory activity of KipI is counteracted by the product of another gene in the operon, KipA. This protein may bind to KipI, preventing its function as an inhibitor of kinase A. KipI may be the first representative of a new class of signal transduction inhibitors that function by direct interaction with the catalytic domain of histidine kinases to counteract signals influencing the "sensor" domain of such kinases. This inhibitor represents yet another way by which the phosphorelay signal transduction system is affected by negative regulators under the control of metabolic, environmental, or cell cycle influences antithetical to the initiation of developmental transcription.

Bacillus subtilis↗
PubMed1997

Systemic lupus erythematosus: clinical expression and anti-Ro/SS--a response in patients with and without lesions of subacute cutaneous lupus erythematosus.

UNLABELLED: Patients with subacute cutaneous lupus erythematosus (SCLE) have recurrent annular and/or psoriasiphorm skin lesions, with or without systemic disease. OBJECTIVE: To analyse the clinical expression and the Ro/SS-A response associated with SCLE in patients with systemic lupus erythematosus (SLE). METHODS: 128 consecutive patients with SLE were studied. Anti-Ro/SS-A antibodies were detected by ELISA, (anti-60 kD Ro/SSA antibodies), immunoblotting (anti-60 kD and anti-52 kD Ro/SS-A antibodies) and counterimmunoelectrophoresis (CIE). RESULTS: Seventeen patients (13.2%) showed SCLE lesions. Photosensitivity was more frequent in patients with SCLE (82%) than in patients without these cutaneous lesions (45%) (OR: 5.6). Arthritis (OR: 6.3), Raynaud's phenomenon (OR: 4.9), pleuritis (OR: 7.6), central nervous system disorder (OR: 6.4), renal disease (OR: 6.3), anemia (OR: 7.9), hypocomplementemia (OR: 6.1) and anti-dsDNA antibodies (OR: 12.7) were significantly more frequent in patients without SCLE. Anti-Ro/SS-A antibodies were detected in 15 (88.2%) patients with SCLE and 62 (55.8%) patients without SCLE by ELISA, in 10 (58.8%) and 34 (30.6%) patients by immunoblotting, and in 13 (76.4%) and 34 (30.6%) by CIE, respectively. Anti-60 kD-Ro/SS-A and anti-La antibodies, but not anti-52 kD-Ro/SS-A, were significantly more frequent in patients with SCLE than in patients without SCLE. CONCLUSIONS: The presence of SCLE lesions in patients with SLE is associated with a more favourable prognosis. The major anti-Ro/SS-A response is directed against the native 60 kD Ro/SS-A protein.

Adult↗
PubMed1996

The relationship of epileptic auras and psychological attributes.

Studies suggest a high frequency of epileptic auras with intellectual content among epileptic patients with psychopathology and personality disorders. This study compared measures of personality and psychosocial functioning between epileptic patients with cognitive auras and epileptic patients with noncognitive auras. Ten patients with complex partial seizures who experienced cognitive auras had consistently more depressive traits and psychosocial difficulties than 50 patients with other psychic or nonpsychic auras, particularly if the patients with cognitive auras had left hemisphere epileptiform foci. Cognitive auras may be associated with depressive traits among epileptic patients. The findings were also in agreement with studies that relate the left hemisphere to depression.

Adult↗
PubMed1996

Antiribonucleoprotein antibodies in children with human immunodeficiency virus infection: comparative study with childhood-onset systemic lupus erythematosus.

UNLABELLED: A number of clinical and laboratory features of human immunodeficiency virus (HIV) infection are found in systemic lupus erythematosus (SLE). OBJECTIVE: To analyze the presence of circulating antibodies to small nuclear ribonucleoproteins (snRNP) in both diseases. METHODS: We studied sera from 44 HIV-infected children, from 22 patients with childhood-onset SLE, and from 50 healthy children. Anti-snRNP antibodies were detected by (ELISA) using recombinant and affinity-purified nuclear antigens, by counterimmunoelectrophoresis (CIE), and by immunoblotting using extractable nuclear antigens. RESULTS: Anti-snRNP antibodies were detected by ELISA in 30 HIV-infected patients (68.1%) and 19 SLE patients (86.3%). These antibodies were directed against U1-RNP (61.3% and 77.2%), Sm (29.5% and 54.5%), 60kD-Ro/SS-A (47.7% and 50%), and La/SS-B proteins (18.1% and 9%), respectively. None of the HIV-infected children and 11 SLE patients (50%) showed anti-snRNP antibodies by CIE. None of the HIV-infected patients showed anti-70 kD U1-RNP or anti-D-Sm antibodies by immunoblotting. No differences between the two groups were noted relative to the presence of nonprecipitating anti-snRNP antibodies. No such reactivities were observed among the normal sera tested. CONCLUSIONS: Nonprecipitating anti-snRNP antibodies in HIV-infected children are as frequent as in childhood-onset SLE. The significance of these antibodies is not clear at present. Perhaps they are polyreactive and low-affinity antibodies and a mechanism of molecular mimicry may explain these results; however, we cannot exclude a specific stimulation of B-cells by nuclear antigens.

Adolescent↗
PubMed1995

The use of Japanese and bobwhite quail as indicator species in avian toxicity test. ECPA/GIFAP Environmental Round Table.

A comparative analysis was made between the toxicity of plant protection products to two species of quail used in regulatory testing. It was shown that in general differences in the sensitivity between bobwhite quail and Japanese quail were small, and not statistically significant. It was therefore concluded that both species should be seen as equally suitable models for avian safety assessment. The mutual acceptance of studies carried out on either of these species for US and EC registration procedures, would lead to a reduction in vertebrate sacrifice and resource spending.

Animals↗
PubMed1994

DNA supercoiling and thermal regulation of unsaturated fatty acid synthesis in Bacillus subtilis.

Bacillus subtilis growing at 37 degrees C synthesizes, almost exclusively, saturated fatty acids. However, when a culture growing at 37 degrees C is transferred to 20 degrees C, the synthesis of unsaturated fatty acids is induced. The addition of the DNA gyrase inhibitor novobiocin specifically prevented the induction of unsaturated fatty acid synthesis at 20 degrees C. Furthermore, it was determined that plasmid DNA isolated from cells growing at 20 degrees C was significantly more negatively supercoiled than the equivalent DNA isolated from cells growing at 37 degrees C. The overall results agree with the hypothesis that an increase in DNA supercoiling associated with a temperature downshift could regulate the unsaturated fatty acids synthesis in B. subtilis.

Bacillus subtilis↗
PubMed1994

Autoimmune phenomena in children with human immunodeficiency virus infection and acquired immunodeficiency syndrome.

We have studied sera from 44 children with Human Immunodeficiency Virus infection and Acquired Immunodeficiency Syndrome using immunoblotting, radioimmunoassay, enzymoimmunoassay and indirect immunofluorescence. We have detected a low incidence of antinuclear (2.9%), anti-reticulin (2.9%) and anti-smooth muscle (14.7%) antibodies by indirect immunofluorescence. By enzymoimmunoassay we have detected anti-dsDNA (20.5%) and anti-ENA [anti-nRNP (61.3%), anti-Sm (29.5%), anti-Ro (47.7%) and anti-La (18.1%)] antibodies. Tests for anti-dsDNA by radioimmunoassay were negative, suggesting the presence of low-avidity anti-DNA antibodies. By immunoblotting we have detected anti-C (nRNP) (33.3%), anti-BB' (Sm) (33.3%), anti-Ro (60 KD) (4.5%) and anti-La (11.3%) antibodies. The presence of anti-Ro antibodies was associated with progressive neurological disease. Long-term follow-up studies with larger numbers of patients are necessary to evaluate the clinical significance of the presence of anti-dsDNA and anti-ENA antibodies in children infected with Human Immunodeficiency Virus.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Heterogeneity of the anti-Ro(SSA) response in rheumatic diseases.

OBJECTIVE: The immune response to the Ro(SSA) antigen is heterogeneous. Anti-Ro(SSA) positive sera may contain antibodies recognizing either a 60 or a 52 kDa polypeptide component of the Ro(SSA) particle. Thus we sought to determine the profile of anti-Ro(SSA) antibodies defined by immunoblotting in patients with rheumatic diseases. METHODS: Immunoblotting against human placenta extract and ELISA against recombinant Ro(SSA) antigen as confirmatory tests were done to detect anti-Ro(SSA) antibodies in 563 sera from patients with systemic lupus erythematosus (SLE). Sjögren's syndrome (SS), rheumatoid arthritis (RA) and other connective tissue diseases. RESULTS: Anti-52 kDa antibodies were more common in primary patients with SS (9/22; 40.9%) than in patients with SLE (29/135; 21.4%) or patients with RA (7/315; 2.2%). Anti-60 kDa antibodies were more frequent in patients with SLE (26/135; 19.2%) than in patients with primary SS (2/22; 9%) or RA (17/315; 5.3%). None of the 22 patients with primary SS had only antibodies to the 60 kDa polypeptide. Among the 153 patients whose sera were positive by ELISA, 73 (47.7%) were negative by immunoblotting. The most frequent diagnoses in these sera were RA and SLE. The anti-52 kDa sera had higher optical density values compared to anti-60 kDa sera. CONCLUSIONS: Our observations indicate the existence of qualitatively and quantitatively different anti-Ro(SSA) responses in the rheumatic diseases. The major responses are anti-52 kDa antibodies in primary SS, both anti-52 and anti-60 kDa antibodies in SLE, and anti-60 kDa antibodies in RA and other connective tissue diseases.

Antibodies, Antinuclear↗
PubMed1993

Effects of bis(tri-n-butyltin)oxide in Japanese quail exposed during egg laying period: an interlaboratory comparison study.

The guideline no. 206 for testing of chemicals of the Organization for Economic Cooperation and Development (OECD) comprising an avian reproduction test using the Japanese quail (Coturnix coturnix japonica; Termminck and Schlegel 1849) as pair-hold test organisms has been applied in a version that reduced the treatment period to 6 weeks without any pretreatment. In the present study bis(tri-n-butyltin)oxide, C.A. No. 56-35-9 (tributyltin oxide, TBTO) was examined by five participants in an interlaboratory comparison test. A comparable regimen of dosing was performed by all participants starting either with 24 or 60 mg/kg TBTO in the feed and ending with 150 or 375 mg/kg. Within this dose range no signs of toxicity in adults were observed. Substance-related effects however were obvious with regard to egg production, fertility, hatching success, and survival of 14 day-old chicks. A clear dose dependency was given regarding effects on egg weight and on hatchability. The no-observed-effect concentrations for these two parameters was 60 mg/kg TBTO, characterizing these parameters as the most sensitive in this investigation. With the presented set of test parameters further aspects of subchronic toxicity in adults and chicks can be assessed as well as the validity of the performed test. Comparing the results for most test parameters consistency is obvious, thus confirming the applicability of the presented test guideline.

Animals↗
PubMed1993

Regulation of the synthesis of unsaturated fatty acids by growth temperature in Bacillus subtilis.

Bacillus subtilis synthesizes, almost exclusively, saturated fatty acids, when grown at 37 degrees C. When cultures were transferred from 37 degrees C to 20 degrees C, a chloramphenicol- and rifampicin-sensitive synthesis of a C-16 unsaturated fatty acid was observed. Synthesis of this compound reached a plateau after 5 h at 20 degrees C, reaching levels of 20% of the total fatty acid content. [14C]-labelled fatty acids attached as thioesters to acyl-carriers compounds, such as coenzyme A (CoA) or acyl-carrier protein (ACP) synthesized de novo by glycerol-requiring auxotrophs deprived of glycerol to arrest phospholipid synthesis, could not be desaturated at 20 degrees C. Desaturation of these fatty acids was readily observed when glycerol was restored to the cultures allowing resumption of transfer of acyl-moieties from acyl-thioesters to phospholipid. It was also observed that depletion of the pools of CoA and ACP by starvation of pantothenate auxotrophs had no effect on the observed synthesis of unsaturated fatty acid at 20 degrees C. The overall results indicate that synthesis of unsaturated fatty acids in B. subtilis is a cold-inducible process and that phospholipids are obligate intermediates in this fatty acid desaturation pathway.

Acetyl Coenzyme A↗