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Biomedical subjects

R A Gomes

Publications and source records attributed to R A Gomes.

At least 19 recordsLinked to original sources
PubMed2006

Measurement of the K0 charge radius and a CP-violating asymmetry and a search for CP-violating E1 direct photon emission in the rare decay KL--> pi+ pi- e+ e-.

Using the complete KTeV data set of 5,241 candidate K(L)--> pi(+) pi(-) e(+) e(-) decays (including an estimated background of 204 +/- 14 events), we have measured the coupling g(CR)= 0.163 +/- 0.0149(stat) +/- 0.023(syst) of the CP conserving charge radius process and from it determined a K(0) charge radius of = [-0.077 +/- 0.007(stat) +/- 0.011(syst)]fm(2). We have determined a first experimental upper limit of 0.04 (90% C.L.) /g(e1)/ / /g(M1)/ of the couplings for the E1 and M1 direct photon emission processes. We also report the measurement of /g(M1)/ including a vector form factor /g(M1)/(1 + (a(1)/a(2))/((M(2)(p)-(M(2)(k))= 2M(K)E(gamma*)), where vector /g(M1)/= 1.11+/- 0.12(stat) +/- 0.08(syst) and a(1)/a(2) = [-0.744 +/- 0.027(stat) +/- 0.032(syst)] GeV(2)/c(2). Finally, a CP-violating asymmetry of [13.6 +/- 1.4(stat) +/- 1.5(syst)]% in the CP and T odd angle phi between the decay planes of the e(+) e(-) and pi(+) pi(-) pairs in the K(L) center of mass is reported.

Journal Article↗
PubMed2005

Observation of the decay xi0 --> sigma+ mu- nu(mu).

The xi0 muon semileptonic decay has been observed for the first time with nine identified events using the KTeV beam line and detector at Fermilab. The decay is normalized to the xi0 beta decay mode and yields a value for the ratio of decay rates gamma(xi0 --> sigma+ mu- nu(mu))/gamma(xi0 --> sigma+ e- nu(e)) of [1.8(-0.5)(+0.7)(stat) +/- 0.2(syst)] x 10(-2). This is in agreement with the SU(3) flavor symmetric quark model.

Journal Article↗
PubMed2004

Search for the rare decay K(L)-->pi(0)e(+)e(-).

The KTeV/E799 experiment at Fermilab has searched for the rare kaon decay K(L)-->pi(0)e(+)e(-). This mode is expected to have a significant CP violating component. The measurement of its branching ratio could support the standard model or could indicate the existence of new physics. This Letter reports new results from the 1999-2000 data set. One event is observed with an expected background at 0.99+/-0.35 events. We set a limit on the branching ratio of 3.5x10(-10) at the 90% confidence level. Combining with the previous result based on the data set taken in 1997 yields the final KTeV result: BR(K(L)-->pi(0)e(+)e(-))<2.8x10(-10) at 90% C.L.

Journal Article↗
PubMed2001

Structure of human uropepsin at 2.45 A resolution.

The molecular structure of human uropepsin, an aspartic proteinase from the urine produced in the form of pepsinogen A in the gastric mucosa, has been determined by molecular replacement using human pepsin as the search model. Crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 50.99, b = 75.56, c = 89.90 A. Crystallographic refinement led to an R factor of 0.161 at 2.45 A resolution. The positions of 2437 non-H protein atoms in 326 residues have been determined and the model contains 143 water molecules. The structure is bilobal, consisting of two predominantly beta-sheet lobes which, as observed in other aspartic proteinases, are related by a pseudo-twofold axis. A model of the uropepsin-pepstatin complex has been constructed based on the high-resolution crystal structure of pepsin complexed with pepstatin.

Amino Acid Sequence↗
PubMed2001

Molecular model for the binary complex of uropepsin and pepstatin.

The three-dimensional structure of human uropepsin complexed with pepstatin has been modelled using human pepsin as a template. Uropepsin is an aspartic proteinase from the urine, produced in the form of pepsinogen A in the gastric mucosa. The structure is bilobal, consisting of two predominantly beta-sheet lobes which, as observed in other aspartic proteinases, are related by a pseudo twofold axis. A structural comparison between binary complexes of pepsin:pepstatin and uropepsin:pepstatin is discussed.

Binding Sites↗
PubMed1998

Purification and partial characterization of cathepsin D from porcine (Sus scrofa) liver using affinity chromatography.

Cathepsin D, a lysosomal aspartic protease, has been purified from porcine liver using a combination of pepstatin-A agarose and Affi-Gel Blue affinity chromatography, followed by size-exclusion chromatography. The purified protein consists of two polypeptide chains of 15 and 30 kDa, and has an isoelectric point of 6.8. Porcine liver cathepsin D has maximum activity at pH 2.5-3.0 as determined by its activity against hemoglobin, with a Kcat of 14.3 s-1 and a kcat/KM of 2.70 x 10(6) s-1M-1 as determined by the hydrolysis of a fluorogenic peptide substrate.

Animals↗
PubMed1998

Crystallization, preliminary X-ray analysis and Patterson search of a new aspartic protease isolated from human urine.

Aspartic protease (EC 3.4.23) make up a widely distributed class of enzymes in animals, plants, microbes and, viruses. In animals these enzymes perform diverse functions, which range from digestion of food proteins to very specific regulatory roles. In contrast the information about the well-characterized aspartic proteases, very little is known about the corresponding enzyme in urine. A new aspartic protease isolated from human urine has been crystallized and X-ray diffraction data collected to 2.45 A resolution using a synchrotron radiation source. Crystals belong to the space group P2(1)2(1)2(1). The cell parameters obtained were a = 50.99, b = 75.56 and c = 89.90 A. Preliminary analysis revealed the presence of one molecule in the asymmetric unit. The structure was determined using the molecular replacement technique and is currently being refined using simulated annealing and conjugate gradient protocols.

Aspartic Acid Endopeptidases↗
PubMed1997

Correlation between adrenal central vein parasitism and heart fibrosis in chronic chagasic myocarditis.

The correlation between Trypanosoma cruzi parasitism of the adrenal central vein (ACV) wall and fibrous connective tissue neoformation in the left ventricular myocardium (LVM) of patients with chronic Chagas' disease who were autopsied was evaluated using the following procedures: 1) a comparison of the incidence of fibrosis in the LVM among 18 chagasic patients with ACV parasitism and 18 individuals without phleboparasitism; 2) a determination of fibrosis intensity in the LVM in 12 cases with ACV parasites and in 12 cases without phleboparasitism, matched with respect to age, sex, race, and anatomoclinical form of the disease (indeterminant, cardiac, and digestive forms); and 3) in the cases with ACV parasitism, a calculation of Pearson's correlation coefficient between T. cruzi nests in the vessel and the intensity of fibrous connective tissue neoformation in the LVM. Among chagasic individuals with adrenal phleboparasitism, there was an increased incidence and intensity of fibrous connective tissue neoformation in the LVM, both highly significant, compared with patients without adrenal phleboparasitism. Furthermore, there was a positive, though nonsignificant, correlation (r = +0.19) between the density of nests in the ACV and the intensity of myocardial fibrosis. These results are consistent with previous data showing a higher intensity of the leukocyte exudate in the LVM and increased heart weight in individuals with T. cruzi nests in the ACV, suggesting a role of parasitism at that site in terms of the development of chronic chagasic cardiopathy.

Adrenal Glands↗
PubMed1997

Characterization of kininogenase activity of an acidic proteinase isolated from human kidney.

An acidic proteinase was purified from human kidney cortex. The enzyme showed a molecular mass of 31 kDa by SDS-PAGE, 36 kDa by gel filtration, and isoelectric points of 5.2 and 6.1. The optimum pH for hydrolysis of bovine hemoglobin was about 3.5. Reverse-phase HPLC analysis of the incubation mixture of the enzyme with human plasma showed the presence of an active peptide on rat uterus muscle with the same retention time as the methionyl-lysyl-bradykinin (MLBK) standard. The specific activities were 2.91 micrograms MLBK equivalent mg-1.min-1 at pH 3.5 and 2.15 micrograms MLBK equivalent mg-1.min-1 at pH 6.0. All the enzymatic activities of this human kidney proteinase were inhibited by pepstatin A. Intramolecularly quenched fluorogenic substrates with amino acid sequences of human kininogen were used to determine the cleavage points. On the N-terminal sequences (Abz-Leu-Met-Lys-Arg-Pro-Eddnp and Abz-Met-Ile-Ser-Leu-Met-Lys-Arg-Pro-Eddnp) the cleavage occurred at the Leu-Met linkage, and on the C-terminal sequences (Abz-Phe-Arg-Ser-Ser-Arg-Eddnp and Abz-Phe-Arg-Ser-Ser-Arg-Gln-Eddnp) the cleavage occurred at the Arg-Ser linkage. Abz-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-Ser-Ser-Arg-Gln-Eddnp++ + was hydrolyzed by the renal acidic proteinase and yielded the peptide Abz-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg (Abz-bradykinin). Kinectic parameters were determined using Abz-Met-Ile-Ser-Leu-Met-Lys-Arg-Pro-Eddnp (K(m) = 0.69 +/- 0.08 microM; Kcat = 0.052 +/- 0.0095 s-1; Kcat/K(m) = 0.075 +/- 0.005 microM-1.s-1) and Abz-Phe-Arg-Ser-Ser-Arg-Gln-Eddnp (K(m) = 1.56 +/- 0.16 microM; Kcat = 0.0048 +/- 0.0001 s-1; Kcat/K(m) = 0.003 +/- 0.0003 microM-1.s-1). Human liver cathepsin D had no activity on C-terminal sequences and human pepsin hydrolyzed them at the Ser-Ser bond. The results suggest that the renal acid proteinase is distinct from human pepsin and human liver cathepsin D and releases MLBK from human kininogen.

Amino Acid Sequence↗
PubMed1992

Intramolecularly quenched fluorogenic peptide substrates for human renin.

Six intramolecularly quenched fluorogenic peptides related to the sequences Phe8 to His13, His6 to His13, and Tyr4 to His13 of the human angiotensinogen, containing o-aminobenzoyl (Abz) and ethylenediamine dinitrophenyl (EDDnp) groups at amino- and carboxyl-terminal amino acids residues, were synthesized by classical solution methods. The Leu-Val is the only bond of all obtained peptides that was hydrolyzed by human renin with different degrees of purity and was resistant to hydrolysis by pig renin and cathepsin D. The hydrolysis of Abz-His-Pro-Phe-His-Leu-Val-Ile-His-EDDnp by human renin was inhibited by a highly specific transition-state analog of angiotensinogen (IC50 = 7.8 x 10(-9) M), described by K. Iizuka et al. (1990, J. Med. Chem. 33, 2707-2714). Therefore, specific and sensitive substrates for the continuous assay of human renin in which as little as 70 microGU of human renin could be detected by Abz-Phe-His-Leu-Val-Ile-His-EDDnp were described. The optimal pHs of hydrolysis of the substrates were in the range 4 to 6.

Amino Acid Sequence↗
PubMed1979

Modification of a mathematical model for survival curves in photobiology.

A modification of the Haynes' mathematical model (1966) can be suggested as a result of bacterial UV-survival experiments carried out. A new equation is proposed: lnS = Fi(x), + Fr(x), wherein x is the radiation dose, Fi(x) = -- kox describes how radiation damage is produced on the cell and Fr(x) = (krec + kc)x + Re(x) describes how repair systems act. ko is the relative inactivation efficiency of radiation on each cell. krec is the recombination recovery system efficiency. kc gives the additional repair increasing per cell when excision and recombination systems act simultaneously. Re(x) = a(1-e-bs) describes solely the excision repair process. The asymptote of non-exponential curves intercepts the survival fraction axis on the ordinate so (extrapolated point). In the modified model a=lnSo instead of a=So (Haynes' model).

Bacteria↗
PubMed1979

Some repair effectiveness coefficients as indicators of E. coli UV-resistance.

Mathematical studies of E. coli survival curves to UV (254 nm) lead to the definition of a photoresistance parameter - the "mean survival dose" (MSD) - to compare radiation resistances of genetically related bacterial strains. Based on this MSD-parameter some repair coefficients were proposed as indicators of the relative effectiveness with which every repair system recovers radiation lesions in cells. The theoretical values calculated for the proposed coefficients are in agreement with those which were obtained from experimental data presented in the literature.

DNA Repair↗