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Biomedical subjects

R Grau

Publications and source records attributed to R Grau.

At least 19 recordsLinked to original sources

Gene algebra from a genetic code algebraic structure.

By considering two important factors involved in the codon-anticodon interactions, the hydrogen bond number and the chemical type of bases, a codon array of the genetic code table as an increasing code scale of interaction energies of amino acids in proteins was obtained. Next, in order to consecutively obtain all codons from the codon AAC, a sum operation has been introduced in the set of codons. The group obtained over the set of codons is isomorphic to the group (Z(64), +) of the integer module 64. On the Z(64)-algebra of the set of 64(N) codon sequences of length N, gene mutations are described by means of endomorphisms f:(Z(64))(N)-->(Z(64))(N). Endomorphisms and automorphisms helped us describe the gene mutation pathways. For instance, 77.7% mutations in 749 HIV protease gene sequences correspond to unique diagonal endomorphisms of the wild type strain HXB2. In particular, most of the reported mutations that confer drug resistance to the HIV protease gene correspond to diagonal automorphisms of the wild type. What is more, in the human beta-globin gene a similar situation appears where most of the single codon mutations correspond to automorphisms. Hence, in the analyses of molecular evolution process on the DNA sequence set of length N, the Z(64)-algebra will help us explain the quantitative relationships between genes.

Anticodon↗

Laparoscopic ventral hernia repair: postoperative antibiotics decrease incidence of seroma-related cellulitis.

Seroma formation has been documented as a common complication in laparoscopic ventral herniorraphy. However, there are no recent studies documenting the incidence of or protective strategies against seroma-related cellulitis. The purpose of this study was to evaluate 65 laparoscopic ventral herniorraphies and to determine if seroma-related cellulitis can be prevented by the routine use of postoperative prophylactic antibiotics. A retrospective case review of 65 laparoscopic ventral herniorraphies was done at our institution from February 2002 to January 2004. All were performed using either Gore-Tex DualMesh or Bard Composix mesh and performed under the direct supervision of a single surgeon. Twenty patients received only preoperative third-generation cephalosporins or fluoroquinolones. All other patients received either 7 days of postoperative oral cephalosporins or fluoroquinolones in addition to preoperative antibiotics. Sixty-five patients underwent laparoscopic ventral hernia repair. There were 45 patients in the postoperative antibiotic group and 20 patients in the preoperative-only antibiotic group. Twenty-one patients developed seromas. Twelve of these developed cellulitis. The rates of seroma formation were similar in the two groups with 30 per cent in the preoperative only group and 33 per cent in the postoperative antibiotic group. However, 100 per cent of the seromas in the preoperative antibiotic group developed seroma-related cellulitis. Only 40 per cent of seromas in the postoperative antibiotic group developed cellulitis. In addition, two seromas in the preoperative antibiotics-only group progressed to frank mesh infection necessitating operative removal. There were no complications related to antibiotic administration. Laparoscopic ventral hernia repair is a safe and effective procedure. Our seroma rate is 30 per cent and compares equally with prior reported studies. Seroma-related cellulitis is a common problem that can lead to mesh infection, postoperative morbidity, and further need for operative care. The administration of 7 days of postoperative prophylactic antibiotics appears to be a safe and effective means to limit seroma-related cellulitis.

Antibiotic Prophylaxis↗

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↗

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↗

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↗

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↗

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↗

[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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗