Sexually transmitted infection as a cause of anal cancer

BACKGROUND: The incidence of anal cancer has increased in recent decades, particularly among women. To identify underlying risk factors, we conducted a population-based case-control study in Denmark and Sweden. METHODS: We conducted telephone interviews with 324 women and 93 men in whom invasive or in situ anal cancer was diagnosed between 1991 and 1994, 534 controls with adenocarcinoma of the rectum, and 554 population controls. The interviews covered a wide spectrum of possible risk factors for anal cancer. Odds ratios were calculated by logistic regression. Specimens of anal-cancer tissue and samples of rectal adenocarcinomas were tested for human papillomavirus (HPV) DNA with the polymerase chain reaction. RESULTS: Multivariate analysis revealed consistent and statistically significant associations between measures of sexual promiscuity and the risk of anal cancer in both men and women. There was a significant trend toward an association between higher numbers of partners of the opposite sex in women (P<0.001) and men (P<0.05) and strong associations with a variety of venereal diseases. In women, receptive anal intercourse, particularly before the age of 30 years, and venereal infections in the partner were also associated with an increased risk (odds ratios, 3.4 and 2.4, respectively). Fifteen percent of the men with anal cancer reported having had homosexual contact, as compared with none of the controls (P<0.001). High-risk types of HPV, notably HPV-16, were detected in 84 percent of the anal-cancer specimens examined, whereas all rectal-adenocarcinoma specimens tested were negative for HPV. CONCLUSIONS: Our study provides strong evidence that a sexually transmitted infection causes anal cancer. The presence of high-risk types of HPV, notably HPV-16 (which is known to cause cancer of the cervix), in the majority of anal-cancer tissue specimens suggests that most anal cancers are potentially preventable.     

Race/ethnicity, social class, and prevalence of breast cancer prognostic biomarkers: a study of white, black, and Asian women in the San Francisco bay area

We assessed distributions of breast cancer prognostic biomarkers by race/ethnicity and socioeconomic position among paraffin-embedded tumor biopsy specimens from 135 US women (48 white women, 44 black women, 43 Asian women) diagnosed with breast cancer between 1966 and 1990. No racial/ethnic or socioeconomic differences in distributions were observed for tumor stage, lymph node involvement, estrogen, progesterone, and epidermal growth factor receptors, oncogenes such as Her2/neu and p53, cytoplasmic proteins cathepsin-D and ps2, and two indices of cell growth, Ki67 and DNA ploidy, adjusting for age at diagnosis, menopausal status, place of birth and, for racial/ethnic comparisons, working class composition of census block-group at diagnosis. Black and Asian women, however, were 3.5 times (95% confidence interval [CI] = 1.2, 10.1) and 3.7 times (95% CI = 1.3, 10.6), respectively more likely than white women to have a tumor size of > or = 20 mm, and Asian women were 3.4 times (95% CI = 1.1, 10.4) more likely than black women to be positive for androgen receptor, adjusting for these same factors. No differences in distributions by socioeconomic position were observed for these latter two tumor characteristics. These data suggest that racial/ethnic and socioeconomic disparities in breast cancer survival are unlikely to be explained solely by differential distributions of molecular breast cancer prognostic biomarkers.     

Energy transfer in LHCII monomers at 77K studied by sub-picosecond transient absorption spectroscopy

Energy transfer from chlorophyll b (Chl b) to chlorophyll a (Chl a) in monomeric preparations of light-harvesting complex II (LHCII) from spinach was studied at 77 K using pump-probe experiments. Sub-picosecond excitation pulses centered at 650 nm were used to excite preferentially Chl b and difference absorption spectra were detected from 630 to 700 nm. Two distinct Chl b to Chl a transfer times, approximately 200 fs and 3 ps, were found. A clearly distinguishable energy transfer process between Chl a molecules occurred with a time constant of 18 ps. The LHCII monomer data are compared to previously obtained LHCII trimer data, and both data sets are fitted simultaneously using a global analysis fitting routine. Both sets could be described with the following time constants: 140 fs, 600 fs, 8 ps, 20 ps, and 2.9 ns. In both monomers and trimers 50% of the Chl b to Chl a transfer is ultrafast (<200 fs). However, for monomers this transfer occurs to Chl a molecules that absorb significantly more toward shorter wavelengths than for trimers. Part of the transfer from Chl b to Chl a that occurs with a time constant of 600 fs in trimers is slowed down to several picoseconds in monomers. However, it is argued that observed differences between monomers and trimers should be ascribed to the loss of some Chl a upon monomerization or a shift of the absorption maximum of one or several Chl a molecules. It is concluded that Chl b to Chl a transfer occurs only within monomeric subunits of the trimers and not between different subunits.     

High affinity presentation of an autoantigenic peptide in type I diabetes by an HLA class II protein encoded in a haplotype protecting from disease

Tissue composition and the distribution of body mass are described for four genera of East African Bovidae (Madoqua, Gazella, Damaliscus, Hippotragus) with supporting data from four others (Neotragus, Oryx, Tragelaphus, Connochaetes). These species are high in muscle mass, an adaptation convergent with other high-speed terrestrial cursors, bounders, and saltators. The segments below the elbow/cubitus and knee/stifle/genu joints in small bovids are both lighter in percent of total body mass (8.6% TBM) and less heavily muscled (10-15% of total limb musculature) than those segments in macaques (13.6% TBM, 20-25% of the limb musculature). Bovid species differ from one another in the regional distribution of muscle mass. Madoqua kirkii (4-5 kg) concentrates muscle in the lumbar extensors and hindlimbs; large species such as Damaliscus doreas (50-60 kg) and Hippotragus niger (160-220 kg) distribute it more evenly between the lumbar and cervical regions and between the hindlimbs and forelimbs. Gazella dorcas (10-20 kg) is quantitatively intermediate in those characteristics. The redistribution of muscle mass with increasing size correlates with the loss of axial bending of the vertebral column: in small, hindlimb dominant, 'dorsomobile' species such as Madoqua sagittal mobility increases stride length through 'extended' suspension; in large 'dorsostable' species such as Damaliscus and Hippotragus the vertebral column resists bending, consequently abbreviating or omitting this non-contact phase of the gait cycle. Locomotor adaptation as it is reflected in size, shape, and musculoskeletal structure is the key to habitat choice, dietary specialization, social structure, and male agonistic behavior and, therefore, central to the fabric of behavioral ecology.     

Allylmercapturic acid as urinary biomarker of human exposure to allyl chloride

OBJECTIVE: To evaluate the use of urinary mercapturic acids as a biomarker of human exposure to allyl chloride (3-chloropropene) (AC). During three regular shut down periods in a production factory for AC, both types of variables were measured in 136 workers involved in maintenance operations. METHODS: Potential airborne exposure to AC was measured by personal air monitoring in the breathing zone. In total 205 workshifts were evaluated. During 99 workshifts no respiratory protection equipment was used. Mercapturic acid metabolites were measured in urinary extracts by gas chromatography-mass spectrometry (GC-MS). RESULTS: During 86 work shifts when no respiratory protection was used the air concentrations of AC were below the Dutch eight hour time weighted average (8 h-TWA) occupational exposure limit (OEL) of AC (3 mg/m3), whereas in 13 workshifts the potential exposure, as measured by personal air monitoring, exceeded the OEL (3.3 to 17 mg/m3). With the aid of GC-MS, 3-hydroxypropylmercapturic acid (HPMA) was identified as a minor and allylmercapturic acid (ALMA) as a major metabolite of AC in urine samples from the maintenance workers exposed to AC. The concentrations of ALMA excreted were in a range from < 25 micrograms/l (detection limit) to 3550 micrograms/l. The increases in urinary ALMA concentrations during the workshifts correlated well with the 8h-TWA air concentrations of AC (r = 0.816, P = 0.0001, n = 39). Based on this correlation, for AC a biological exposure index (BEI) of 352 micrograms ALMA/g creatinine during an eight hour workshift is proposed. In some urine samples unexpectedly high concentrations of ALMA were found. Some of these could definitely be attributed to dermal exposure to AC. In other cases garlic consumption was identified as a confounding factor. CONCLUSION: The mercapturic acid ALMA was identified in urine of workers occupationally exposed to airborne AC and the increase in ALMA concentrations in urine during a workshift correlated well with the 8 h-TWA exposure to AC. Garlic consumption, but not smoking, is a potential confounding factor for this biomarker of human exposure to AC.     

Germ-cell mutagenesis in lambda lacZ transgenic mice treated with ethylating and methylating agents: comparison with specific-locus test

Germ-cell mutagenesis has been studied in male lambda lacZ transgenic mice in such a way that the data can be compared with literature data for germ-cell mutagenesis obtained with the specific-locus test (SLT). Mutagenesis induced by ethylnitrosourea (ENU), ethylmethanesulphonate (EMS), methylnitrosourea (MNU) and methylmethanesulphonate (MMS), has been studied in mature spermatozoa isolated from the epididymis and vas deferens. In order to investigate mutagenesis in different phases of spermatogenesis, animals were sacrificed at various time points after treatment. ENU at 150 mg/kg body weight significantly induced mutations in stem cells (analysis at 100 days post-treatment), but not in post-stem cells (7 days post-treatment). EMS (250 mg/kg) and MMS (60 mg/kg) induced mutations only in post-stem cells (7 days), but not in stem cells (100 days). MNU (70 mg/kg) resulted in an increase of mutations in both post-stem cells (14 and 37 days) and stem cells (100 days), although the latter, due to a limited number of data, was not statistically significant. All these data are in accordance with published SLT data. These results indicate that lambda lacZ transgenic mice are a suitable model to study gene mutations in different phases of spermatogenesis.     

Single-laser approach for fluorescence guidance of excimer laser angioplasty at 308 nm: evaluation in vitro and during coronary angioplasty

BACKGROUND AND OBJECTIVE: Spectroscopic guidance of laser angioplasty has been attempted using a diagnostic He-Cd laser in addition to the therapeutic laser system. This study evaluated a single-laser approach for simultaneous ablation and fluorescence excitation. STUDY DESIGN/MATERIALS AND METHODS: A spectroscopy system was coupled to a clinical XeCl excimer laser. Ablation of 162 human aortic samples in saline and blood with 45 mJ/mm2 per pulse yielded 676 fluorescence spectra validated histologically. The same equipment was used in 16 patients for angioplasty of 18 coronary stenoses applying 500 to 1,725 pulses with 45 to 60 mJ/mm2 under saline flushing. A total of 783 spectra were recorded and validated by intracoronary ultrasound (categories: atheroma, fibrous plaque, calcified lesion). RESULTS: In vitro, 5 types of spectra could be differentiated: (1) atheroma, (2) fibrous plaque, (3) calcified lesion in saline, (4) media, and (5) calcified lesion in blood. Discriminant analysis prospectively classified 576 validation spectra with the following sensitivity and specificity for each type: (1) 83.5 and 97.1%, (2) 85.7 and 96.8% (3) 100 and 98.5%, (4) 98.1 and 99.3%, (5) 98.9 and 100%, respectively. In vivo type 1, 2, 3, and 5 spectra were also observed, but not the media spectrum. The predominant sonographic category also prevailed in spectroscopy. Calcified lesions yielded type 3 and 5 as well as mixed spectra. CONCLUSIONS: Using an excimer laser for angioplasty allows combining ablation and fluorescence excitation without a diagnostic laser. Principal types of atherosclerotic lesions and the media can be differentiated spectroscopically with this approach.     

Predicting the earnings of supported employees with mental retardation: a longitudinal study

A random sample (N = 197) of supported employees with mental retardation was examined in a longitudinal study. Results indicate that intelligence, prior earnings, and federal job subsidy predicted future earnings. Statistical controls applied to the stratified sample show that job placement, job type, subsidy, and means of transportation had little influence on earnings.     

Immunohistochemical and molecular characterization of the rat 11 beta-hydroxysteroid dehydrogenase type II enzyme

Mineralocorticoid action is facilitated by 11 beta-hydroxysteroid dehydrogenase type II (11 beta HSD2), which metabolizes glucocorticoids and allows aldosterone to bind to the nonselective mineralocorticoid receptor. We have recently demonstrated the presence of the 11 beta HSD2 protein in a wide range of human epithelia, suggesting that it is the sole isoform endowing specificity in man. In the present study we have used an immunopurified polyclonal antibody (RAH23) raised against a C-terminal peptide derived from the cloned rat 11 beta HSD2 protein to perform immunohistochemical and molecular analysis in rat tissues. In frozen sections of rat kidney, strong staining was seen with the RAH23 antibody in the distal tubule; weaker staining was observed in the thick ascending loop of Henle and the medullary and papillary collecting ducts. Punctate cortical staining was observed in the fetus at 20 days gestation and in 8-day-old rats, with a noticeable increase in the staining pattern at 16 days of age. The kidney did not attain the adult pattern of staining until 28 days of age. Epithelia of ileum and colon also stained with RAH23, as did excretory ducts of the submandibular gland. Intrahepatic and excretory bile ducts displayed strong immunoreactivity in the epithelial lining. Rat adrenal glands showed evidence of the 11 beta HSD2 antigen in the zona fasciculata and zona reticularis, but not in the zona glomerulosa or medulla. Western blot analysis with the RAH23 antibody revealed strong bands in the kidney, colon, adrenal gland, and submandibular gland at 40 kDa, colinear with the migration of the cloned 11 beta HSD2 enzyme. A band of medium intensity was also seen at this size in the pancreas, whereas a band of moderate intensity was seen in the bile duct, and weaker bands were noticed in the stomach, small intestine, and liver, with a diffuse band at 36-42 kDa in the prostate. Strong bands were seen in the pancreas and prostate at 78 kDa, with weaker signals in the colon, adrenal, stomach, and bile duct. A number of tissues also displayed multiple bands at about 30 kDa. Enzymatic assays on tissue homogenates showed extensive conversion of corticosterone to its 11-dehydro product in an NAD-dependent manner in the submandibular gland, adrenal gland, and kidney, but not in the pancreas or prostate. This study confirms the ubiquitous presence of 11 beta HSD2 in sodium-transporting epithelia, demonstrates the high level of 11 beta HSD2 protein and enzyme activity in the rat adrenal, and suggests a possible role for the enzyme in the biliary system. Further studies are required to determine the relevance of the various molecular species to the activity, latency, and processing of the enzyme.     

Integral measurements with a plutonium inert matrix fuel rod in a heterogeneous light water reactor lattice

As part of PSI's validatory efforts for neutronics calculations pertaining to inert matrix fuel (IMF) deployment in light water reactors, first-of-their-kind integral measurements have been carried out at the PROTEUS facility employing a specially fabricated Pu-Er-Zr IMF rod in a heterogeneous (boiling water reactor) test lattice. Analogous experiments have also been conducted with MOX and “dummy” IMF rods, providing the basis for a systematic comparison of experimental and calculational results.