Homozygous single nucleotide polymorphism of the complement C1QA gene is associated with decreased levels of C1q in patients with subacute cutaneous lupus erythematosus.

We report an association between a non-familial form of photosensitive Lupus-specific skin disease, subacute cutaneous lupus erythematosus (SCLE), and a new single nucleotide polymorphism (SNP) in the C1QA gene. We also describe an association between this SNP and lower levels of serum C1q. This SNP consists of adenine replacing the third guanine in the codon for aminoacid residue Gly70 (position excludes the 22 amino acid leading peptide) that is located in the second exon of the C1QA gene. We have designated this SNP C1qA-Gly70GGA (the GenBank sequence at this location is C1qA-Gly70GGG). A survey of 19 SCLE patients showed that 11 (58%) were homozygous for C1qA-Gly70GGA SNP, seven (37%) were heterozygous, and only one patient (5%) was homozygous for the GenBank sequence. In contrast, only 13 of 62 (21%) normal controls were homozygous for the C1qA-Gly70GGA SNP, 41 (66%) controls were heterozygous and eight (13%) controls were homozygous for the GenBank sequence. Thus, the C1qA-Gly70GGA SNP is strongly associated with SCLE (P-value = 0.005 by chi-square analysis with Yates correction). This SNP would traditionally be classified as clinically silent as it does not encode a different amino acid. However, our studies have suggested that this SNP appears to be associated with a functional abnormality of C1q expression since its presence correlates inversely with serum levels of C1q antigenic protein in both SCLE patients and normal controls. The mechanism by which this phenotypic change is associated with the translationally silent (synonymous) ClqA-Gly70GGA genetic variation is currently unknown.

Evolutionarily conserved, "acatalytic" carbonic anhydrase-related protein XI contains a sequence motif present in the neuropeptide sauvagine: the human CA-RP XI gene (CA11) is embedded between the secretor gene cluster and the DBP gene at 19q13.3.

Conserved amino acid motifs are found in numerous expressed genes. Proteins and peptides with functional relationships may be identified using probes designed to hybridize with these motifs. An oligonucleotide probe was prepared to match the sequence of the expected active region of a frog corticotropin-releasing factor-like peptide sauvagine and used to screen a sheep brain cDNA library. A novel 1331-bp cDNA encoding a putative 328-residue protein with a theoretical mass of 36 kDa was identified. The presence of a strong signal sequence indicates that it is a secreted protein. The amino- and carboxy-terminal regions are characterized by several potential phosphorylation sites and binding motifs, suggesting a role in intracellular signal transduction. Although the protein possesses a 7-residue sequence identical to that found in sauvagine, its overall primary structure most closely resembles those of the alpha-carbonic anhydrases (alpha-CAs). Moreover, the detection of the human and mouse orthologues in the EST databases, together with an evolutionary analysis, indicates that the protein represents a new member of the alpha-CA gene family, which we designate carbonic anhydrase-related protein XI (CA-RP XI), encoded by CA11 (human) and Car11 (mouse, rat). The human CA11 gene appears to be located between the secretor type alpha(1,2)-fucosyltransferase gene cluster (FUT1-FUT2-FUT2P) and the D-site binding protein gene (DBP) on chromosome 19q13.3. Despite potentially inactivating changes in the active-site residues, CA-RP XI is evolving very slowly in mammals, a property indicative of an important function, which has also been observed in the two other "acatalytic" CA isoforms, CA-RP VIII and CA-RP X, whose functions are unknown.

Successful repair of postoperative ascending aortic mycotic false aneurysms using circulatory arrest.

Mediastinal wound infections following open-heart operations are successfully managed in most patients by aggressive debridement and placement of substernal drainage catheters or application of omental or muscle flaps. Nonetheless, the involvement of foreign bodies, such as felt pledgets adjacent to cardiac structures, can result in infections that persist despite flap coverage and can present as mycotic false aneurysms of the ascending aorta. We present the cases of 3 patients who underwent successful repair of such aneurysms late after surgical treatment of mediastinal wound infections. We describe our technique of repair using groin cannulation for bypass, moderate hypothermia, and circulatory arrest to improve exposure and minimize bleeding.

Cronkhite-Canada syndrome associated with colon carcinoma and adenomatous changes in C-C polyps.

A 73-yr-old man with the clinical features of Cronkhite-Canada syndrome developed colonic carcinoma. Radiologic and endoscopic examination revealed numerous polyps involving the stomach and large intestine. Histologic examination of the biopsied polyps revealed polypoidal lesions covered by a single layer of normal columnar mucus-secreting epithelial cells. The stroma of each polyp was composed of well-vascularized edematous lamina propria containing inflammatory cells and glands of variable sizes. Some of the glands were cystically dilated and lined by a single layer of mucin-secreting epithelial cells. These polyps were reminiscent of "juvenile polyps" or retention polyps. Some of these polyps also showed definite adenomatous changes at the surface epithelium. In addition, a large cecal tubulovillous adenoma with foci of well-differentiated adenocarcinoma was noted, indicating that adenomatous and carcinomatous epithelial changes can occur in otherwise nonneoplastic polyposis of the Cronkhite-Canada syndrome as seen in the present case.

Sinus bradycardia associated with peripheral lipids and total parenteral nutrition.

This case report describes a 23-yr-old woman with Crohn's disease who developed sinus bradycardia 4 hr after initiation of total parenteral nutrition with lipids through a peripheral vein. The bradycardia persisted for 1 wk, with only slight improvement when the lipids were held for two 4-hr periods. The heart rate began to improve when lipids were changed from 10 to 20%, and continued to rise after Synthroid was started. The possible relationships between nutritional and thyroid status, as well as lipids and heart rate are discussed.