Genomic variation of human papillomavirus type 16 and risk for high grade cervical intraepithelial neoplasia

BACKGROUND: Epidemiologic studies have demonstrated strong and consistent associations between the detection of human papillomavirus (HPV) type 16 DNA and the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. However, HPV16 is also the most common type of HPV in the normal population, and only a minority of women with HPV16 infection develop cervical cancer. Studies of genomic heterogeneity in HPV16 have demonstrated the presence of multiple variant forms in all human populations examined to date. It is conceivable that the natural variants of HPV16 in a given population may not have the same biologic behavior. PURPOSE: This study was designed to determine the association between natural variants of HPV16 and the risk of biopsy-confirmed CIN 2 or 3, the most important precancerous lesions of the uterine cervix. METHODS: Prospective studies were conducted among 1) women attending a university and 2) women presenting to a sexually transmitted disease clinic. Subjects were eligible for inclusion in this investigation if the initial cytologic findings did not reveal CIN 2-3 and HPV16 DNA was detected by means of a polymerase chain reaction (PCR)-based method in one or more cervical or vulvovaginal samples. Eligible subjects were followed every 4 months with cervical Pap smears and colposcopic examinations. Women were referred for biopsy if cytology or colposcopy suggested CIN 2-3. Two groups of HPV16 variants, prototype-like and nonprototype-like, were determined by means of single-strand conformation polymorphism (SSCP) analysis of PCR products from the noncoding region of the viral genome. Representative SSCP patterns from HPV16 variants were further characterized by direct DNA sequencing of the PCR products. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox regression analysis. RESULTS: Prototype-like variants accounted for 79% of the HPV16 detected in university students and 86% of the virus detected in patients presenting to the sexually transmitted disease clinic. CIN 2-3 was confirmed by biopsy in nine of 57 HPV16-positive women attending the university and in 10 of 66 HPV16-positive women presenting to the sexually transmitted disease clinic. Among university students, those with HPV16 nonprototype-like variants were 6.5 (95% CI = 1.6-27.2) times more likely to develop CIN 2-3 than those with prototype-like variants. A similar association was observed among women presenting to the sexually transmitted disease clinic (RR = 4.5; 95% CI = 0.9-23.8). CONCLUSIONS: This study suggests that the risk of developing CIN 2-3 is not the same with all variants of HPV16 and that nonprototype-like variants confer a greater risk compared with prototype-like variants. The important genomic differences underlying this increased risk of CIN 2-3 remain to be determined.     

Ornithine decarboxylase activity in muscle, liver, and intestinal tissue of turkeys during a short-term feed withdrawal and following refeeding

The activity of ornithine decarboxylase (ODC), an enzyme associated with cellular growth and protein synthesis, was examined in breast muscle, liver, and intestinal tissues of turkeys during a short-term period of feed withdrawal (FW) and following refeeding. Turkeys from a randombred control line were reared under standard management practices to 3 wk of age in battery brooders. Feed was then withdrawn from FW birds for a 48-h period, after which feed was consumed ad libitum. Control birds consumed feed ad libitum throughout the test period. Tissues were collected from 12 birds per treatment following 24 and 48 h of FW and at 6, 12, 24, and 48 h following refeeding for later determination of tissue ODC activity. Activity of ODC was greater in tissue from the small intestine than in liver tissue and both had greater activity than that exhibited by breast muscle. Short-term FW and refeeding produced differential responses in ODC activity of the three tissues examined. Feed withdrawal resulted in a reduction of ODC activity in intestinal tissue, whereas activity was unaffected for liver or breast muscle tissues. Compensatory increases in ODC activity were observed in liver and intestinal tissues; however, the increase was both more rapid and transitory in small intestine than in liver tissue. The ODC activity in breast muscle was largely unaffected by short-term FW and refeeding. Patterns of ODC activity in liver during FW and refeeding closely resembled patterns observed for absolute and relative liver weight. Thus, the results of the present experiment demonstrate that short-term FW and refeeding influence underlying growth mechanisms of supply organs, such as hepatic and intestinal tissue, in addition to affecting overall growth and muscle development.     

Radiofrequency volumetric tissue reduction for treatment of turbinate hypertrophy: a pilot study

BACKGROUND: Apoptosis maintains cell homeostasis. Altered apoptosis is involved in carcinogenesis. It was our aim to investigate whether reflux esophagitis may alter apoptosis in the esophageal mucosa and whether antireflux surgery may restore normal apoptosis. METHODS: Apoptosis was studied preoperatively and postoperatively in esophageal biopsies of 39 patients with various grades of reflux esophagitis and in Barrett's mucosa using the TUNEL method. Biopsies were also taken from lesions of the squamous epithelium adjacent to the Barrett's mucosa. RESULTS: Apoptosis increased with the severity of esophagitis. Apoptosis was low in Barrett's epithelium. Squamous epithelium adjacent to Barrett's mucosa showed increased apoptosis. After surgery apoptosis decreased in squamous epithelium, and it remained low in Barrett's epithelium. CONCLUSIONS: Apoptosis in reflux esophagitis may be protective against increased proliferation. Low apoptosis following antireflux surgery indicates that surgery is effective to prevent reflux-induced cell proliferation. Inhibition of apoptosis in Barrett's may promote carcinogenesis. This may not change following surgery.     

Catheter-based radiotherapy to inhibit restenosis after coronary stenting

BACKGROUND: In animal models of coronary restenosis, intracoronary radiotherapy has been shown to reduce the intimal hyperplasia that is a part of restenosis. We studied the safety and efficacy of catheter-based intracoronary gamma radiation plus stenting to reduce coronary restenosis in patients with previous restenosis. METHODS: Patients with restenosis underwent coronary stenting, as required, and balloon dilation and were then randomly assigned to receive catheter-based irradiation with iridium-192 or placebo. Clinical follow-up was performed, with quantitative coronary angiographic and intravascular ultrasonographic measurements at six months. RESULTS: Fifty-five patients were enrolled; 26 were assigned to the iridium-192 group and 29 to the placebo group. Angiographic studies were performed in 53 patients (96 percent) at a mean (+/-SD) of 6.7+/-2.2 months. The mean minimal luminal diameter at follow-up was larger in the iridium-192 group than in the placebo group (2.43+/-0.78 mm vs. 1.85+/-0.89 mm, P=0.02). Late luminal loss was significantly lower in the iridium-192 group than in the placebo group (0.38+/-1.06 mm vs. 1.03+/-0.97 mm, P=0.03). Angiographically identified restenosis (stenosis of 50 percent or more of the luminal diameter at follow-up) occurred in 17 percent of the patients in the iridium-192 group, as compared with 54 percent of those in the placebo group (P= 0.01). There were no apparent complications of the treatment. CONCLUSIONS: In this preliminary, short-term study of patients with previous coronary restenosis, coronary stenting followed by catheter-based intracoronary radiotherapy substantially reduced the rate of subsequent restenosis.     

Monoclonal antibodies to the alpha-subunit of the putative human H+,K+-ATPase encoded by the atp1al1 gene

The N-terminal fragment of ATP1AL1, the possible catalytic subunit of human ouabain-sensitive H+,K(+)-ATPase, was expressed in Escherichia coli cells as two recombinant proteins: the Ser14-Ile104 fragment or the same fragment containing His6 sequence at its N-end. The second protein was purified by metal-affinity chromatography and used as an antigen to construct two hybridoma lines producing antibodies of the IgM class. These monoclonal antibodies were shown to recognize not only the starting antigen but also the full-size recombinant ATP1AL1 protein and do not react with Na+,K(+)-ATPase.