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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The generation of oxygen free radicals by peripheral blood monocytes and neutrophils of patients with rheumatic fever and rheumatic heart disease has been studied using luminol enhanced chemiluminescence technique. Five groups of patients; acute rheumatic fever, recurrence of rheumatic activity, chronic rheumatic heart disease, acute pharyngitis and normal controls were studied. In all groups except the controls, measurements were made on 0, 15, 90 and 180 days. The chemiluminescence was measured in response to streptococcal membrane antigen, carbohydrate antigen and latex as triggering agents. Chemiluminescent response of monocytes, as well as, neutrophils was significantly higher (P less than 0.01) in acute rheumatic fever and recurrence of rheumatic heart disease as compared to patients with acute pharyngitis and chronic rheumatic heart disease through the study period and with all the triggering agents. A significant decline (P less than 0.001) in chemiluminescence was observed from day 0 to day 180 in the acute rheumatic fever, recurrence of rheumatic heart disease and pharyngitis patients while no such change, was observed in the chronic rheumatic heart disease group. This study raises the possibility that these phagocytic cells, which infiltrate the myocardium, may have a role in the pathogenesis of cardiac disease seen in patients with rheumatic heart disease, through the generation of oxygen free radicals.
J Mol Cell Cardiol 1990 Jun
PMID:Role of oxygen free radicals generated by blood monocytes and neutrophils in the pathogenesis of rheumatic fever and rheumatic heart disease. 223 34

Sera from 50 patients with chronic rheumatic heart disease were analysed by an enzyme linked immunosorbent assay for the presence of antibodies to the streptococcal minimal adjuvant moiety, muramyl dipeptide (MDP). The T-cell responsiveness to this structure was also studied in vitro, using the lymphocyte transformation test. Fifty four percent of the patients possessed anti-MDP antibodies in their sera when examined 5 to 25 years after the initial rheumatic attack. Such antibodies were found only in 5 to 6% of sera from healthy controls or from patients with cardiac disease of non-rheumatic origin. There was neither antigenic nor mitogenic stimulation by MDP of the T-cells from peripheral blood of chronic rheumatic heart disease patients or controls. The results point to a lifetime persistence of anti-MDP antibodies in rheumatic fever and rheumatic heart disease. Possible mechanisms by which detectable levels of such antibodies are maintained in rheumatic heart disease are discussed.
J Mol Cell Cardiol 1989 Jan
PMID:Antibodies to a streptococcal cell wall adjuvant structure persist in patient with chronic rheumatic heart disease. 278 3

The Rel family of transcription factors participate in a diverse array of processes, including acute responses to injury and infection, lymphocyte differentiation, and embryonic patterning. These proteins show homology in an extended region spanning about 300 amino acids (the Rel homology domain [RHD]). The RHD mediates both DNA binding and interactions with a family of inhibitor proteins, including I kappa B alpha and cactus. Previous studies have shown that an N-terminal region of the RHD (containing the sequence motif RXXRXRXXC) is important for DNA binding, while the C-terminal nuclear localization sequence is important for inhibitor interactions. Here we present a structure-function analysis of the Drosophila dorsal RHD. These studies identify another sequence within the RHD (region I) that is essential for inhibitor interactions. There is a tight correlation between the conservation of region I sequences and the specificity of Rel-inhibitor interactions in both flies and mammals. Point mutations in the region I sequence can uncouple DNA binding and inhibitor interactions in vitro. The phenotypes associated with the expression of a modified dorsal protein in transgenic Drosophila embryos suggest a similar uncoupling in vivo. Recent crystallographic studies suggest that the region I sequence and the nuclear localization sequence might form a composite surface which interacts with inhibitor proteins.
Mol Cell Biol 1995 Jul
PMID:Specificity of Rel-inhibitor interactions in Drosophila embryos. 779 70

Placement of ten different anti-streptococcal monoclonal antibody (mAb) secreting hybridoma cells, as well as positive and negative controls into animals and sacrificing on a daily basis showed a difference in the tissue sites of accumulating mAb as noted by fluorescent antibody testing. Initial binding of the mAb was noted by day two on the kidney GBM in all the animals. Striated muscle tissues tested positive starting at day nine with only four of the mAbs, by which time the GBM was strongly positive. Fluorescent antibody testing of heart and skeletal muscle from animals in which one of the polyreactive IgM mAb secreting hybridoma cell lines was placed showed a distinctive staining of the Z-lines. Indirect fluorescent and immunoperoxidase testing as well as competitive blocking experiments confirmed the reactivity of this mAb for the Z-line of heart and skeletal muscle. Immunodots and Western blots along with direct and blocking assays confirmed that the critical cross-reactive Z-line antigen was alpha-actinin, supporting the concept that this anti-SCM mAb was reactive both in vivo and in vitro. These results confirm the cross-reactive nature of anti-SCM antibodies for mammalian tissue and bear important implications on the etiology of post-streptococcal glomerulonephritis and rheumatic heart disease.
Res Commun Mol Pathol Pharmacol 1995 Aug
PMID:Tracking the in vivo localization of streptococcal cell membrane (SCM) monoclonal antibodies: potential model for post-streptococcal sequelae. 855 77

Almost exactly 50 years ago, R. A. Fisher and R. Race proposed a model for the evolution of the RH (rhesus) genes in which the less common haplotypes were derived from the commoner ones by recombination, and in which the gene order was D-C-E. No direct-evidence bearing on this model was available then, and has not been until now. Here we present evidence for non-reciprocal intergenic exchange (gene conversion) occurring once in human history to generate the common RHCE allele, Ce. We have also used new polymorphisms to construct haplotypes which suggest that intragenic recombination played a major role in the generation of the less common haplotypes, but only if RHD lies 3' of RHCE, i.e. the order is C-E-D. We provide both genetic and physical evidence supporting this arrangement.
Hum Mol Genet 1997 Jun
PMID:Evolution of the human RH (rhesus) blood group genes: a 50 year old prediction (partially) fulfilled. 917 29

The evolution of the RH gene family is characterized by two major duplication events, the first one originating the RH50 and RH30 genes and the second one giving rise to RHCE and RHD, the two paralogous RH30 genes which encode the Rh blood group antigens in human. The new sequence data obtained here for mouse RH50 and RH30 and for macaque RH50 allowed us to compare the evolutionary rates of the two genes and to show that RH50 evolved about 2.6 times more slowly than RH30 at nonsynonymous positions. This result implies that Rh50 proteins were evolutionarily more conserved compared to Rh30 polypeptides, thus being indicative of the functional significance of the former protein in species as distantly related as sponge and human. The duplication event leading to RH50 and RH30 genes was estimated to have occurred between 250 and 346 million years ago. Moreover, we could also estimate that the duplication event producing the RHCE and RHD genes occurred some 8.5 +/- 3.4 million years ago, in the common ancestor of human, chimpanzee, and gorilla. Interestingly, this event seems to coincide with the appearance in these species of a G-to-T mutation in the RH50 gene which created a stop codon in the corresponding transcript. This led to an Rh50 C-terminal cytoplasmic domain shorter than that found in orangutan and early primates.
J Mol Evol 1999 Feb
PMID:The members of the RH gene family (RH50 and RH30) followed different evolutionary pathways. 992 83

Increased Plasma Nitrite Level in Cardiac Failure. Nitric oxide is implicated in the pathogenesis of cardiac failure. Plasma nitrite level (an end product of nitric oxide metabolism) is studied in 15 patients of chronic rheumatic valvular heart disease with myocardial contractile dysfunction and cardiac failure (Group I), 15 patients of chronic rheumatic valvular heart disease with similar valvular lesions, normal myocardial contractile function and without cardiac failure (Group II) and 15 healthy controls (Group III). Patients in Group I had higher nitrite level (242.2+/-31.7 n m) compared to Group II (142.6+/-24.4 n m) and Group III (102.7+/-15.9 n m). Among the patients with rheumatic heart disease, increasing nitrite level correlated significantly with worsening of contractile function [Nitrite v End systolic volume/Body surface area (T(xy.z)=0.23), Nitrite v End systolic dimension/Body surface area (T(xy.z)=0.32), Nitrite v left ventricular ejection fraction (T(xy.z)=-0.24), Nitrite v tricuspid annular plane systolic excursion (T(xy.z)=-0. 29)] and worsening New York Heart Association (NYHA) functional class (r(s)=0.5). We conclude that plasma nitrite, a stable end product of nitric oxide metabolism is increased in patients of rheumatic valvular heart disease with cardiac failure, suggesting increased nitric oxide production. Increased level of nitric oxide might be playing a significant role in myocardial contractile dysfunction and alteration of vascular response in cardiac failure.
J Mol Cell Cardiol 1999 Aug
PMID:Increased plasma nitrite level in cardiac failure. 1042 47

By amplification and sequencing of RH gene intron 4 of various primates we demonstrate that an Alu-Sx-like element has been inserted in the RH gene of the common ancestor of humans, apes, Old World monkeys, and New World monkeys. The study of mouse and lemur intron 4 sequences allowed us to precisely define the insertion point of the Alu-Sx element in intron 4 of the RH gene ancestor common to Anthropoidea. Like humans, chimpanzees and gorillas possess two types of RH intron 4, characterized by the presence (human RHCE and ape RHCE-like genes) or absence (human RHD and ape RHD-like genes) of the Alu-Sx element. This led us to conclude that in the RH common ancestor of humans, chimpanzees, and gorillas, a duplication of the common ancestor gene gave rise to two genes, one differing from the other by a 654-bp deletion encompassing an Alu-Sx element. Moreover, most of chimpanzees and some gorillas posses two types of RHD-like intron 4. The introns 4 of type 1 have a length similar to that of human RHD intron 4, whereas introns 4 of type 2 display an insertion of 12 bp. The latest insertion was not found in the human genome (72 individuals tested). The study of RH intron 3 length polymorphism confirmed that, like humans, chimpanzees and gorillas possess two types of intron 3, with the RHD-type intron 3 being 289 bases shorter than the RHCE intron 3. By amplification and sequencing of regions encompassing introns 3 and 4, we demonstrated that chimpanzee and gorilla RH-like genes displayed associations of introns 3 and 4 distinct to those found in man. Altogether, the results demonstrate that, as in humans, chimpanzee and gorilla RH genes experienced intergenic exchanges.
Mol Biol Evol 2000 Jan
PMID:Rh gene evolution in primates: study of intron sequences. 1066 12

Nuclear factor-kappaB (NF-kappaB) and the glucocorticoid receptor (GR) are transcription factors with opposing actions in the modulation of immune/inflammatory responses. NF-kappaB induces the expression of proinflammatory genes, while GR suppresses immune function in part by suppressing expression of the same genes. Previously, we demonstrated that physiological antagonism between NF-kappaB and GR is due to a mutual transcriptional antagonism that requires the p65 subunit of NF-kappaB and multiple domains of GR (1). To elucidate the mechanism(s) of NF-kappaB p65 and GR transcriptional antagonism, we analyzed the interactions of wild-type p65 and p65 RHD (rel homology domain, a dominant negative mutant of p65 which lacks a transactivation domain) with GR. We show that p65RHD blocks p65-mediated transactivation, yet does not block the repression of GR transactivation by p65, indicating that transcriptional activity by p65 is not required to repress GR function. Both p65 and p65 RHD physically interact with GR, but only intact p65 represses GR-mediated signaling, implicating the p65 transactivation domain in the transcriptional repression of GR. To further characterize p65-GR interactions, we examined the role of the transcriptional co-integrator CREB binding protein (CBP) in their mutual antagonism. GR-mediated repression of p65 transactivation and p65-mediated repression of GR transactivation, as well as the physical interaction between NF-kappaB and GR, are enhanced by CBP. GR bound to the antagonist RU 486, although transcriptionally inactive, retains the ability to repress p65 transactivation. However, CBP does not physically interact with antagonist-bound GR and does not enhance its repressive effect on p65. These data suggest that CBP functions as an integrator of p65/GR physical interaction, rather than as a limiting cofactor for which p65 and GR compete.
Mol Endocrinol 2000 Aug
PMID:CBP (CREB binding protein) integrates NF-kappaB (nuclear factor-kappaB) and glucocorticoid receptor physical interactions and antagonism. 1093 46

L-Carnitine plays a role in the utilization of fatty acids and glucose in the myocardium. Previous studies have indicated carnitine deficiency in patients with congestive heart failure. However, the extent of altered carnitine metabolism and left ventricular function is not fully determined. This study is designed to determine if plasma L-carnitine levels can serve as a marker for impaired left ventricular function in patients with congestive heart failure. To test this hypothesis, plasma and urinary levels of L-carnitine were measured in 30 patients with congestive heart failure (CHF) and in 10 control subjects. CHF was due to dilated cardiomyopathy (DCM) and rheumatic heart disease (RHD). Cardiac functions such as percentage of fractional shortening (%FS), ejection fraction (EF), left ventricular mass index (LVMI), were determined by echocardiography. All patients and control subjects had normal renal functions. Plasma carnitine was significantly higher in patients with DCM (37.05+/-7.62, p < 0.0001) and with RHD (47.2+/-8.04, p < 0.0001) vs. the control subjects (14.4+/-5.30 mg/L). Urinary carnitine was significantly higher in DCM (49.13+/-14.11, p < 0.0001) and in RHD 43.53+/-15.5, p < 0.0001), than the control (25.1+/-5.78 mg/L). Plasma carnitine level correlated significantly with impaired left ventricular systolic functions in these patients: % FS < 25 % (r = -0.38 and p = 0.038), EF < 0.55 (r = -0.502 and p = 0.005) and LMVI > 124 gm/m2 (r = 0.436, and p = 0.016). These data suggest that elevated plasma and urinary carnitine levels in patients with CHF could serve as a marker for myocardial damage and impaired left ventricular functions.
Mol Cell Biochem 2000 Oct
PMID:Plasma carnitine levels as a marker of impaired left ventricular functions. 1112 56


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