Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with Arizonae hinshawii infection of an atherosclerotic abdominal aortic aneurysm is described to emphasize the similarity of the nonenteric infections of man by Arizona and Salmonella organisms. These genera are similar bacteriologically, ecologically, and clinically. This case emphasizes the need for thoroughly considering the differential diagnosis when encountering cryptic bacteremia with either organism.
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PMID:Arizona hinshawii infection of an atherosclerotic abdominal aorta. 721

A loss of function mutation of the CYP19 aromatase gene leads to excess circulating androgens in the fetus and in the mother, resulting in ambiguous genitalia in the female fetus. Later on, lack of aromatase is responsible for sexual infantilism, primary amenorrhea, tall stature, and multicystic ovaries, even in preadolescent girls. Up to now, 11 CYP19 aromatase point mutations and 10 well-documented cases have been reported. In the present case, we are reporting the clinical and hormonal follow-up, from birth to 7 yr of age, of an affected girl with ambiguous genitalia. Gene analysis showed that she was a compound heterozygote for two new CYP19 aromatase point mutations. In the father's allele, there was a consensus 5' splice donor sequence mutation, GAA-AAA at cDNA position bp 655 in exon 5, which probably results in a cryptic donor site. In the mother's allele, there was a base A deletion in exon 9 (Delta A GLU 412X), causing a frame shift mutation, and a stop codon after 98 bp (33 codons) downstream, altering the critical heme-binding region. Basal serum LH and FSH levels were high at 8 d of age (42.9 and 51.3 U/liter), 26 d of age (76.2 and 119 U/liter), and 60 d of age (58.7 and 150 U/liter, respectively). Both gonadotropins dropped dramatically between the second and fifth months of age (to 1.79 and 14.9 U/liter) but remained higher than in normal control girls (0.64 and 8.5 U/liter, respectively). Serum testosterone (T) and androstenedione (Delta(4)A) levels were high during the first month, but Delta(4)A was normal at 2 months of age. However, at 5 months of age, along with significant decrements of serum LH and FSH levels and increments in serum Delta(4)A and T levels, a large ovarian cyst was removed from each gonad. Relatively high levels of T [27.3 ng/ml (94.6 nmol/liter); control, 34.9 ng/ml (121 nmol/liter)], but not of estradiol [1.8 ng/ml (6.6 nmol/liter); control 62.9 ng/ml (231 nmol/liter)], and a high T/estradiol ratio [15.2; control < 1] were found in the follicular fluid. Serum Delta(4)A and T levels remained normal from 1-5 yr of age, but they were high at the last visit (late prepuberty). A GnRH test was performed at 3.9, 6, and 7.1 yr of age. At 3.9 yr, a low prepubertal serum LH peak (2.12 U/liter) was found, but at the older ages, higher serum LH peaks (8.25 and 22.5 U/liter, respectively) were observed. Growth pattern and body mass index were normal, but after the age of 5.2 yr, delays in bone age greater than 2 yr were observed. We concluded that: 1) these two new CYP19 aromatase gene mutations are responsible for the phenotype of aromatase deficiency; 2) in girls, aromatase deficiency results in a decrease of the negative feedback of both serum LH and FSH, which can be detected as early as the second week after birth and persists up to the sixth month of life, and of FSH during the rest of prepuberty; and 3) because large ovarian cysts developed when serum LH and FSH dropped, aromatization of androgens might be required to prevent formation of cystic ovaries.
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PMID:Hypothalamic-pituitary-ovarian axis during infancy, early and late prepuberty in an aromatase-deficient girl who is a compound heterocygote for two new point mutations of the CYP19 gene. 1460 38

The role of matrix metalloproteinases (MMPs) in the pathogenesis of abdominal aortic aneurysm (AAA) has focused on the degradation of the extracellular matrix (ECM). The new frontier of MMP biology involves the role of MMPs in releasing cryptic fragments and neoepitopes from the ECM and the impact of MMPs on the regulation of the inflammatory response. The ECM is a complex structure, much more important than an inert scaffold. Both MMP-2 and MMP-9 expose a cryptic epitope that controls angiogenesis. MMPs inhibit angiogenesis through the release of endostatin, endorepellin, arresten, canstatin, and tumstatin. Other breakdown products of the ECM include fragments of fragmin and elastin degradation products (EDPs). In addition, the ECM contains embedded vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-beta). Inflammation is a complex, highly regulated system that involves the identification of injury or infection, response to the injury or infection, repair and healing, and return to normal homeostasis. In some instances, the inflammatory process leads to a pathologic process that is damaging to the host. MMPs play an important role in the control of the inflammatory response through the modification of proinflammatory cytokines, chemokines, and shedding of membrane receptors. Genetic association studies have been performed to help determine the genetic risk associated with certain single nucleotide polymorphisms (SNPs) However, because of the variability in the patient populations and the size of the population, it is difficult to draw any conclusions from these studies. While the etiology of AAA remains unknown, understanding of the inflammatory process and its regulatory points will develop new strategies for the treatment of AAA. Perhaps one difficulty with understanding the pathogenesis of AAA is the lack of precise definition of the phenotype.
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PMID:Abdominal aortic aneurysm as a complex multifactorial disease: interactions of polymorphisms of inflammatory genes, features of autoimmunity, and current status of MMPs. 1718 28

The hexameric AAA-ATPase, Cdc48p, catalyzes an array of cellular activities, including endoplasmic reticulum (ER)-associated degradation (ERAD), ER/Golgi membrane dynamics, and DNA replication. Accumulating data suggest that unique Cdc48p partners, such as Npl4p-Ufd1p and Ubx1p/Shp1p (p47 in vertebrates), target Cdc48p for these diverse functions. Other Cdc48p-associated proteins have been identified, but the interplay among these factors and their activities is largely cryptic. We now report on a previously uncharacterized Cdc48p-associated protein, Ydr049p, also known as Vms1p, which binds Cdc48p at both the ER membrane and in the cytosol under non-stressed conditions. Loss of YDR049 modestly slows the degradation of the cystic fibrosis transmembrane conductance regulator but does not impede substrate ubiquitination, suggesting that Ydr049p acts at a postubiquitination step in the ERAD pathway. Consistent with Ydr049p playing a role in Cdc48p substrate release, ydr049 mutant cells accumulate Cdc48p-bound ubiquitinated proteins at the ER membrane. Moreover, YDR049 interacts with genes encoding select UBX (ubiquitin regulatory X) and UFD (ubiquitin fusion degradation) proteins, which are Cdc48p partners. Exacerbated growth defects are apparent in some of the mutant combinations, and synergistic effects on the degradation of cystic fibrosis transmembrane conductance regulator and CPY*, which is a soluble ERAD substrate, are evident in specific ydr049-ufd and -ubx mutants. These data suggest that Ydr049p acts in parallel with Cdc48p partners to modulate ERAD and other cellular activities.
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PMID:A Cdc48p-associated factor modulates endoplasmic reticulum-associated degradation, cell stress, and ubiquitinated protein homeostasis. 2114 5

Plasmids PL6A and PL6B are both carried by the C23T strain of the square archaeon Haloquadratum walsbyi, and are closely related (76% nucleotide identity), circular, about 6 kb in size, and display the same gene synteny. They are unrelated to other known plasmids and all of the predicted proteins are cryptic in function. Here we describe two additional PL6-related plasmids, pBAJ9-6 and pLT53-7, each carried by distinct isolates of Haloquadratum walsbyi that were recovered from hypersaline waters in Australia. A third PL6-like plasmid, pLTMV-6, was assembled from metavirome data from Lake Tyrell, a salt-lake in Victoria, Australia. Comparison of all five plasmids revealed a distinct plasmid family with strong conservation of gene content and synteny, an average size of 6.2 kb (range 5.8-7.0 kb) and pairwise similarities between 61-79%. One protein (F3) was closely similar to a protein carried by betapleolipoviruses while another (R6) was similar to a predicted AAA-ATPase of His 1 halovirus (His1V_gp16). Plasmid pLT53-7 carried a gene for a FkbM family methyltransferase that was not present in any of the other plasmids. Comparative analysis of all PL6-like plasmids provided better resolution of conserved sequences and coding regions, confirmed the strong link to haloviruses, and showed that their sequences are highly conserved among examples from Haloquadratum isolates and metagenomic data that collectively cover geographically distant locations, indicating that these genetic elements are widespread.
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PMID:The PL6-Family Plasmids of Haloquadratum Are Virus-Related. 2987 63