Renal artery involvement in patients of coronary artery disease undergoing coronary angiography--a prospective study.

METHODS: We prospectively studied the angiographic incidence of renal artery stenosis in 1000 consecutive patients who underwent coronary angiography for clinically suspected coronary artery disease since December, 1998. Selective renal arteriography was performed in all the patients (mean age 57 years, 74.6% males) after coronary angiography. RESULTS: Systemic arterial hypertension was present in 52%, 29.1% were smokers, 21% had diabetes and 31.2% had hypercholesterolemia. Significant coronary artery diseases was found in 849 (84.9%) patients. Of the total patient cohort, 103 (10.3%) patients had renal artery disease; 78 (7.8%) had insignificant stenosis (> 50%) and significant renal artery stenosis (< 50%) was identified in 25 (2.5%) patients. Three had bilateral renal artery stenosis. Comparisons were made between renal artery stenosis and risk factor profile. There was no statistically significant association between renal artery stenosis and parameters like diabetes mellitus, hypertension, smoking, lipid levels and serum creatinine. CONCLUSION: In our study, the absolute number of cases with significant renal artery stenosis is small, so no statistical analysis could be performed to demonstrate the relationship of presence of renal artery stenosis with severity of CAD. However patients with severe coronary artery disease or having multiple risk factor showed a trend towards increased prevalence of renal artery stenosis, hence renal angiography should be done for this subset of patients.

Genetic analysis of the DNA-dependent protein kinase reveals an inhibitory role of Ku in late S-G2 phase DNA double-strand break repair.

Two major complementary double-strand break (DSB) repair pathways exist in vertebrates, homologous recombination (HR), which involves Rad54, and non-homologous end-joining, which requires the DNA-dependent protein kinase (DNA-PK). DNA-PK comprises a catalytic subunit (DNA-PKcs) and a DNA-binding Ku70 and Ku80 heterodimer. To define the activities of individual DNA-PK components in DSB repair, we targeted the DNA-PKcs gene in chicken DT40 cells. DNA-PKcs deficiency caused a DSB repair defect that was, unexpectedly, suppressed by KU70 disruption. We have shown previously that genetic ablation of Ku70 confers RAD54-dependent radioresistance on S-G(2) phase cells, when sister chromatids are available for HR repair. To test whether direct interference by Ku70 with HR might explain the Ku70(-/-)/DNA-PKcs(-/-/-) radioresistance, we monitored HR activities directly in Ku- and DNA-PKcs-deficient cells. The frequency of intrachromosomal HR induced by the I-SceI restriction enzyme was increased in the absence of Ku but not of DNA-PKcs. Significantly, abrogation of HR activity by targeting RAD54 in Ku70(-/-) or DNA-PKcs(-/-/-) cells caused extreme radiosensitivity, suggesting that the relative radioresistance seen with loss of Ku70 was because of HR-dependent repair pathways. Our findings suggest that Ku can interfere with HR-mediated DSB repair, perhaps competing with HR for DSB recognition.

Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining chromosomal integrity in vertebrate cells.

Yeast Rad52 DNA-repair mutants exhibit pronounced radiation sensitivity and a defect in homologous re combination (HR), whereas vertebrate cells lacking Rad52 exhibit a nearly normal phenotype. Bio chemical studies show that both yeast Rad52 and Rad55-57 (Rad51 paralogs) stimulate DNA-strand exchange mediated by Rad51. These findings raise the possibility that Rad51 paralogs may compensate for lack of Rad52 in vertebrate cells, explaining the absence of prominent phenotypes for Rad52-deficient cells. To test this hypothesis, using chicken DT40 cells, we generated conditional mutants deficient in both RAD52 and XRCC3, which is one of the five vertebrate RAD51 paralogs. Surprisingly, the rad52 xrcc3 double-mutant cells were non-viable and exhibited extensive chromosomal breaks, whereas rad52 and xrcc3 single mutants grew well. Our data reveal an overlapping (but non-reciprocal) role for Rad52 and XRCC3 in repairing DNA double-strand breaks. The present study shows that Rad52 can play an important role in HR repair by partially substituting for a Rad51 paralog.

DNA repair studies: experimental evidence in support of chicken DT40 cell line as a unique model.

DT40 is a chicken B lymphocyte cell line that exhibits a high ratio of targeted and random integration of transfected DNA constructs. Using the DT40 cell line makes it comparatively easy to disrupt multiple genes in a single cell and to generate conditional targeted mutants including tet-controlled cre-lox-mediated and temperature-sensitive mutants. The DT40 mutants show a strong phenotypic resemblance to murine mutants with respect to genes involved in DNA recombination and repair. Because of these characteristics, DT40 is an attractive model for the analysis of DNA recombination and repair studies in vertebrates despite obvious concerns associated with the use of a transformed cell line that may have certain cell-line-specific characteristics. We present experimental evidence to demonstrate the usefulness of the DT40 cell line as a unique model to study DNA damaging events and their associated repair pathways.

Carotid artery involvement in patients of atherosclerotic coronary artery disease undergoing coronary artery bypass grafting.

BACKGROUND: Patients with concomitant critical carotid and coronary artery disease are at risk of major neurological events while undergoing coronary artery bypass grafting. The presence of carotid artery stenosis increases the stroke rate in the perioperative period. In an effort to reduce the stroke rate, many institutions perform routine preoperative noninvasive assessment of the carotid arteries. METHODS AND RESULTS: We analyzed the clinical and laboratory data of 1,200 patients who underwent coronary artery bypass surgery in the last 2 years. Carotid Doppler was normal in 186 patients (15.5%), and showed <30% stenosis in 796 (66.3%), 30%-50% in 110 (9.2%), 50%-70% stenosis in 64 (5.3%) and critical (>70%) stenosis in 44 (3.7%) patients. Conventional risk factors such as hypercholesterolemia, hypertension, smoking and family history were not independent predictors of carotid artery stenosis. However, diabetes as a risk factor had a significant association with carotid artery disease (79.6% v. 43.8%, p<0.02). There was a trend towards increased prevalence of carotid artery stenosis in patients with > or = 2 risk factors (84.3% v. 68.8%). Patients with significant carotid artery stenosis had severe coronary artery disease (triple-vessel disease 93.3%, left main coronary artery disease 12.0%). Out of 44 patients with critical carotid artery stenosis, 27 were subjected to carotid angiography. Doppler findings correlated well with angiography. Seventeen patients underwent carotid artery intervention. None had any perioperative neurological events. A total of 5 (0.4%) patients had a major stroke. Coronary artery bypass grafting was done in 27 patients with critical stenosis without any intervention. The stroke rate (11.1%) was higher in these patients compared to patients with < 70% carotid artery disease or post-carotid intervention (2.5%) patients. Thus, untreated >70% carotid artery stenosis was associated with a higher stroke rate. CONCLUSIONS: Doppler screening of the carotid artery is helpful in detecting the subgroup of patients at increased risk of stroke. Patients with critical carotid artery stenosis should be subjected to angiography. Prophylactic intervention may reduce the occurrence of stroke in the perioperative period.

Identification of risk factors for specific subsites within the oral and oropharyngeal region--a study of 647 cancer patients.

Studies on site specific risks for oral cancers are few. Present investigation explores the possible role of human sociodemographic factors in causing oral cancer. Majority of patients had poor oral hygiene (85.5%) and belonged to 51-60 years age group (35.7%). Most of the subjects were agriculture workers (30.3%). Tongue and floor of mouth included majority of the affected sites (77.2%). Male to female ratio was highest for tonsil (32.3%) but differed marginally for other subsites. Majority of females used tobacco (81%) while males users of tobacco, alcohol and smoking reported in nearly equal proportions. Tobacco and smoking were found as primary risk factors for several intraoral subsites. However, for tongue, palate and lip no risk factor could be identified from given patients' characteristics. In general, tobacco posed high risk for buccal mucosa and alveolus in comparison to other subsites. Smoking affected tonsil and floor of mouth more than other sites. Alcohol posed more risk for buccal mucosa and floor of mouth than tongue.

Serial echocardiographic assessment of left atrioventricular valve function in young children with ventricular inversion.

BACKGROUND: Regurgitation of the morphologic tricuspid valve (mTV) adversely influences the clinical outcome of patients with ventricular inversion. METHODS AND RESULTS: To evaluate the mTV regurgitation (TR), we reviewed serial echocardiograms for 25 children with ventricular inversion, with and without congenital heart surgery. Patient age was from 6 months to 19.0 (median 5.8) years. Follow-up was from 5 months to 15.0 (median 4.1) years. Initial assessment was at a median 65 days of age; only nine (36%) of 25 had TR. At follow-up, 16 (64%) of 25 had TR, with two requiring valve replacement. The mTV was abnormal in 16 (64%) of 25 patients and in 11 (69%) of 16 TR worsened compared with one (11%) of nine patients with "normal" mTVs. Nine (36%) of 25 had Ebstein's anomaly, three of whom had new TR develop. Of 17 patients who underwent cardiac surgery, 10 (59%) had new or increased TR compared with three (37%) of eight nonoperative patients. After intracardiac repairs, eight (73%) of 11 had increased TR develop compared with two (33%) of six patients after extracardiac surgery. CONCLUSIONS: (1) Young patients with ventricular inversion had TR develop during follow-up, without cardiac surgery. (2) Surgical patients with intracardiac repairs had more TR develop than with extracardiac procedures. (3) Anatomic abnormalities of the mTV were associated with an increased risk of TR developing. These data help elucidate the factors that affect the development of TR in patients with ventricular inversion.

Significance of lymphocytic sister chromatid exchange frequencies in ovarian cancer patients.

Very few studies report the analysis of sister chromatid exchanges in ovarian cancer patients. We tested the null hypothesis that SCE frequency increases with the advancing stages of ovarian cancer and follows a Poisson distribution. As controls we examined age- and sex-matched healthy volunteers who had no such past history. An increased average SCE frequency was observed in ovarian cancer patients (6.34 +/- 0.09) vis-à-vis controls (4.47 +/- 0.12). Further, the data also suggested a stage-wise increase in the SCE frequency.

A rapid silver staining and destaining technique for the nucleolus organizer region.

Silver staining of nucleolar organizing regions (NOR) is common, but a standard protocol is lacking. A modification of a rapid silver nitrate staining technique for NORs is presented here. Advantages of the modified technique include reliability, speed, cost and the fact that it can be carried out in the light.

Left ventricular outflow tract obstruction defined by active three-dimensional echocardiography using rotational transthoracic acquisition.

A rotational data acquisition system was used to create three-dimensional images from thoracic and subxiphoid echocardiographic windows in children with various types of subaortic stenosis. Thirteen patients, ranging in age from 2 days to 17 years, were examined. Subaortic obstruction was caused by a discrete fibrous ridge in six patients, hypertrophic cardiomyopathy in two patients, subaortic tunnel in two patients, and septal malalignment, restrictive VSD, and abnormal suture placement each in one patient. Unique views could be obtained equivalent to surgical or autopsy dissections, and allowed more complete understanding of morphology than conventional imaging techniques.