Airborne polycyclic aromatic compounds contribute to the induction of the tumour-suppressing P53 pathway in wild double-crested cormorants.

Polycyclic aromatic compounds (PACs), including polycyclic aromatic hydrocarbons (PAHs) and PAH-like compounds are known or probable environmental carcinogens released into the environment as a by-product of incomplete combustion of fossil fuels and other organic materials. Studies have shown that exposure to PACs in the environment can induce both genotoxicity and epigenetic toxicity, but few studies have related PAC exposure to molecular changes in free ranging wildlife. Previous work has suggested that double-crested cormorants (Phalacrocorax auritus; DCCO) exhibited a higher incidence of genetic mutations when their breeding sites were located in heavily industrialized areas (e.g., Hamilton Harbour, Hamilton, ON, Canada) as compared to sites located in more pristine environments, such as in Lake Erie. The aim of this study was to determine if airborne PACs from Hamilton Harbour alter the tumour-suppressing P53 pathway and/or global DNA methylation in DCCOs. Airborne PACs were measured using passive air samplers in the Hamilton Harbour area and low-resolution mass spectrometry analysis detected PACs in livers of DCCOs living in Hamilton Harbour. Further hepatic and lung transcriptional analysis demonstrated that the expression of the genes involved in the DNA repair and cellular apoptosis pathway were up-regulated in both tissues of DCCOs exposed to PACs, while genes involved in p53 regulation were down-regulated. However, global methylation levels did not differ between reference- and PAC-exposed DCCOs. Altogether, data suggest that PACs activate the P53 pathway in free-ranging DCCOs living nearby PAC-contaminated areas.

Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study.

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.

Single mode, polarization-independent submicron silicon waveguides based on geometrical adjustments.

In this work, we demonstrate via computer simulation the single mode and zero birefringence conditions for photonic wires with height and width less than 600 nm. We report on the simulation conditions for both single mode and zero birefringence in silicon-on-insulator photonic wires and sub-micron rib waveguides using a 3-dimensional imaginary beam propagation method. The results show that operation in both single mode and zero birefringence is possible under certain circumstances and that the conditions are restricted by fabrication processes where birefringence is strongly dependent upon waveguide dimensions. A matrix of waveguide parameters has been identified at both operating wavelengths of 1310 nm and 1550 nm, which can satisfy single mode and zero birefringence conditions simultaneously. This is to provide a general design rule for waveguides in small dimensions on the order of hundreds of nanometres.

Angiographic morphology and the pathogenesis of unstable angina pectoris.

In 110 patients with either stable or unstable angina, the morphology of coronary artery lesions was qualitatively assessed at angiography. Each obstruction reducing the luminal diameter of the vessel by 50% or greater was categorized into one of the following morphologic groups: concentric (symmetric narrowing); type I eccentric (asymmetric narrowing with smooth borders and a broad neck); type II eccentric (asymmetric with a narrow neck or irregular borders, or both); and multiple irregular coronary narrowings in series. For the entire group, type II eccentric lesions were significantly more frequent in the 63 patients with unstable angina (p less than 0.001), whereas concentric and type I eccentric lesions were seen more frequently in the 47 patients with stable angina (p less than 0.05). Type II eccentric lesions were also present in 29 of 41 arteries in patients with unstable angina compared with 4 of 25 arteries in those with stable angina (p less than 0.0001) in whom an "angina-producing" artery could be identified. Therefore, type II eccentric lesions are frequent in patients with unstable angina and probably represent ruptured atherosclerotic plaques or partially occlusive thrombi, or both. A temporary decrease in coronary perfusion secondary to these plaques with or without superimposed transient platelet thrombi or altered vasomotor tone may be responsible for chest pain in some of these patients with unstable angina.

Angiographic evolution of coronary artery morphology in unstable angina.

As previously reported in acute presentations of unstable angina, an identifiable characteristic coronary artery lesion has been found in about 70% of cases at coronary arteriography. This takes the form of an eccentrically placed convex stenosis with a narrow neck due to one or more overhanging edges or irregular, scalloped borders, or both. To study the evolution of lesions responsible for unstable angina, coronary artery anatomy and morphology on angiography were evaluated in patients with stable angina progressing to unstable angina. Group I comprised 25 patients with a history of stable angina who were restudied after an acute episode of unstable angina and Group II comprised 21 patients with little or no change in symptoms between catheterizations. Progression of coronary disease occurred in 19 (76%) of 25 patients in Group I compared with 7 (33%) of 21 in Group II (p less than 0.001). Of the 25 lesions with progression in Group I, 17 progressed to less than 100% and 8 to 100% occlusion. Eighteen of these 25 lesions in Group I were previously insignificant (less than 50% occlusion on the first catheterization). In contrast, of the eight lesions with disease progression in Group II, only two were previously insignificant while six showed at least 50% occlusion on the initial study. The eccentric lesion was seen in 71% of all lesions with progression to less than 100% occlusion in Group I, but it was not seen in any Group II vessel with progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of progesterone on the invasive properties and tumor growth of progesterone receptor-transfected breast cancer cells MDA-MB-231.

One of the potential therapeutic interventions to hormone-independent breast cancer would be to reactivate the expression of estrogen receptor or progesterone receptor (PR) in the tumor cells so as to render the tumor responsive to the hormones. We have reported previously that progesterone markedly inhibited cell growth and induced remarkable focal adhesions in PR-transfected MDA-MB-231 cells. The aim of this study was to determine the effects of progesterone on the invasive properties and in vivo tumor growth of PR-transfected MDA-MB-231 cells. It was found that progesterone has increased cell resistance to trypsin digestion and increased cell attachment to extracellular matrix proteins, especially laminin and fibronectin. In vitro invasion assays using modified Boyden chambers showed that progesterone increased cell migration through matrix protein-coated membranes. However, Northern blotting analysis demonstrated that progesterone strongly down-regulated (up to 60-fold) the gene expression of urokinase plasminogen activator and increased (up to 5-fold) the expression of tissue-type plasminogen activator in these cells. This pattern of gene regulation suggested an inhibition of cell invasiveness because numerous clinical studies have indicated that low levels of urokinase plasminogen activator and high levels of tissue-type plasminogen activator in breast cancer are associated with favorable prognosis. Furthermore, animal studies showed that progesterone strongly inhibited the tumor formation and growth in Scid mice. After 12 weeks of inoculation, the median weight of tumors in the progesterone-treated group was 25 mg compared with 203 mg in the placebo group (P < 0.001). These results suggest that progesterone may provide effective treatment for estrogen receptor- and PR-negative breast cancer if the PR expression were reactivated. Alternatively, activation of progesterone-mediated molecular pathways in hormone-independent breast cancer may achieve similar therapeutic effects.

Histochemical characterization of the cutaneous involvement of acromegaly.

We evaluated the pathogenesis of skin thickening in three patients with acromegaly. Growth hormone levels were normal in one patient and were elevated in two patients. Skin biopsy specimens were obtained from the forearm. Hematoxylineosin staining showed slight epidermal thinning and, in two of the patients, a small increase in the number of fibroblasts. Selective stains for collagen, elastic, and reticular fibers disclosed normal connective tissue. The most striking abnormality was increased glycosaminoglycan deposition on the slides stained with colloidal iron. Glycosaminoglycan infiltration occurred mostly in the papillary and upper reticular dermis and was not directly related to the simultaneous growth hormone levels. Tissue digestion with specific enzymes identified hyaluronic acid, chondroitin-4- and 6-sulfate, and dermatan sulfate as the most prominent glycosaminoglycans in the dermis. The skin ultrastructure appeared to be preserved on electron microscopy. We conclude that cutaneous mucinoses is the main cause for the thickening of the skin in acromegaly.

Altered skin elastic fibers in hypothyroid myxedema and pretibial myxedema.

Elastic fibers account for 2% of dermal volume and are responsible for normal skin resiliency. We investigated a disorder of the dermal elastic component as the mechanism for the decreased elasticity of skin in myxedema. Skin biopsy specimens were obtained from patients with thyroid diseases and normal subjects matched for age, sex, and biopsy location. Elastic fiber concentration, determined by computerized morphometric analysis of Verhoeff-van Gieson-stained sections, was significantly lower than normal in hypothyroid and pretibial myxedema. The decreased elastin concentration was not a consequence of the glycosaminoglycan infiltration. Ultrastructural studies of myxedematous skin showed wide variability of elastic fiber diameter and decreased microfibrils. Myxedema (hypothyroid and pretibial) is consistently associated with quantitative and qualitative defects of dermal elastic fibers.

Outcome after laparoscopic versus open wedge resection for suspected gastric gastrointestinal stromal tumors: A matched-pair case-control study.

BACKGROUND: Laparoscopic resection of gastric gastrointestinal stromal tumors (GISTs) has been shown by several retrospective studies to be technically feasible and associated with favorable outcomes when compared to the open approach. This study aims to mitigate potential selection bias by performing a case control study of laparoscopic (LWR) versus open wedge resection (OWR) matched by resection type, location and tumor size. METHODS: We retrospectively identified 50 consecutive patients who underwent LWR for a suspected gastric GIST from a prospective database and matched this cohort with 50 patients who underwent OWR. RESULTS: There was no statistical difference between the key baseline clinicopathological features of patients' who underwent LWR versus OWR. Patients who underwent LWR had longer operating times [150 (range, 65-270) minutes vs 92.5 (25-200) minutes, P < .001] but decreased median blood loss [0 (0-300) ml vs 0 (0-1200) ml, P = .015], decreased frequency of intraoperative or postoperative blood transfusion [1 (2%) vs 8 (16%), P = .031], decreased median time to liquid diet [2 (0-5) vs 3 (1-7) days, P < .001], decreased median time to solid diet [3 (1-6) vs 5 (2-11) days, P < .001] and decreased postoperative stay [4 (2-10) vs 4.5 (3-17), P < .001] compared to OWR. There was no difference in oncological outcomes such as frequency of close margins (≤ 1 mm) and recurrence-free survival. CONCLUSION: This matched case-control study provides supporting evidence that LWR results in superior perioperative outcomes compared to OWR without compromising on oncological outcomes.

Role of two-dimensional echocardiography, pulsed, continuous wave color flow Doppler techniques in the assessment of ventricular septal rupture after myocardial infarction.

Two-dimensional echocardiography, pulsed and continuous wave Doppler techniques were used for the evaluation of 15 consecutive patients (9 men, 6 women; mean age 71 years, range 61 to 79) with ventricular septal rupture due to acute myocardial infarction (7 anterior, 8 posterior). Standard and modified off-axis 2-dimensional echocardiographic views from parasternal, apical and subcostal windows correctly identified this defect in 14 of the 15 patients. Pulsed Doppler echocardiography confirmed the presence of left-to-right-sided shunt by showing a high-velocity, aliased, systolic flow and a low-velocity diastolic flow in the right ventricle in 14 patients. Continuous wave Doppler echocardiography showed a high-velocity systolic and low-velocity diastolic flow signal of left-to-right shunt in 14 patients. Color flow Doppler imaging identified a left-to-right shunt in all 6 patients in whom it was performed. Doppler and 2-dimensional echocardiographic studies missed a small apical septal defect in 1 patient with anteroseptal myocardial infarction. Two-dimensional echocardiography correctly diagnosed right ventricular infarction in all 5 patients with posteroinferior infarction. Ventricular septal rupture and/or left-to-right-sided shunt was confirmed in all 15 patients by the following: surgical inspection in 11, necropsy in 3, left ventricular cineangiography in 5 and right-sided heart catheterization and oximetry data in 13 patients. Data indicate that 2-dimensional echocardiography correctly shows the precise location of septal rupture in most patients after acute myocardial infarction and allows assessment of left and right ventricular infarction and function.(ABSTRACT TRUNCATED AT 250 WORDS)

Solitary small active junctional nevi in juvenile patients.

Solitary small very dark and papular pigmented nevi, less than 4 mm, are seen commonly in the second decade of life and have a distinctive histologic pattern. Microscopically these lesions show abundant intraepidermal melanin, included within the keratin layer, and proliferating single melanocytes or nevus cell nests. Prominent nucleoli in the melanocytic cells, occasional mitoses, and the invariable presence of moderate numbers of dermal melanophages and lymphocytes indicated the activity of the pathologic process. The benignity of the lesions in nine patients is supported by a benign course over a one- to three-year evaluation period after limited excisional biopsy procedures. The clinical and pathologic evidence of activity in these nevi suggests yet another possible precursor of malignant melanoma. The B-K mole syndrome and the dysplastic nevi syndrome differ from these cases both clinically and histologically.

Erythematous generalized granuloma annulare.

Two elderly patients had a distinctive generalized, erythematous form of granuloma annulare. The granulomatous changes were shown to be located superficially in the dermis. One patient had diabetes mellitus and carcinoma of the breast. Both patients had pulmonary emphysema.

Clinicopathologic correlations in Alibert-type mycosis fungoides.

Five cases of mycosis fungoides of the Alibert type were studied by taking multiple biopsy specimens at different stages of the disease. Large hyperchromatic, slightly irregular mononuclear cells are the most frequent cells. Ultrastructurally, the cells were only slightly convoluted, had prominent heterochromatin banding at the nuclear membrane, and unremarkable cytoplasmic organelles. Highly convoluted cerebriform nucleated cells were few. Large regular vesicular histiocytes were prominent in the early stages. Ultrastructurally, the cells showed evenly distributed euchromatin. Epidermotrophism was equally as important as Pautrier's abscess as a hallmark of the disease. Stereologic techniques comparing the infiltrate with regard to size and convolution of cells in all stages of mycosis fungoides with infiltrates seen in a variety of benign dermatoses showed no statistically significant differences.

Giant congenital neuroid melanocytic nevus.

A patient with a variety of nevus cell nevi, a congenital giant melanocytic nevus, abnormal facies, vascular anomaly of the leg, and mental retardation was examined. The patient also had neuroid elements within the giant nevus that led to the consideration of neurofibromatosis. Because neurofibromatosis is a genetically determined condition with tissue different from the neuroid elements seen in giant nevi, the two conditions are considered to be different entities. Malignant transformation of congenital giant pigmented nevi occurs, although the incidence of such transformation remains a subject of controversy.

Thin malignant melanomas with regression and metastases.

The significance of partial regression in thin malignant melanomas (0.76 mm or less) of the skin was evaluated to determine if the regression was associated with the later development of metastases in patients who previously were considered to have a favorable prognosis. Of 575 patients with primary cutaneous melanoma treated and followed up by the Division of Surgical Oncology at the University of Illinois, Chicago, we found that 103 (18%) had tumors that measured less than 0.76 mm. Of these, 30 (29%) showed histologic evidence of partial regression. In six (20%) of the 30 patients, visceral metastases developed and the patients died. All six had more than 77% regression of their primary tumors. Of the remaining 24 patients, only one had regression greater than 77% and she is still alive three years after diagnosis. Most of these 24 (83%) patients had regression of less than 50% (mean, 29.9%). No metastasis occurred in the 73 patients who had thin melanomas without histologic evidence of regression. It is apparent from this study that patients with thin melanomas who show partial regression cannot be included in the "low-risk" group if the extent of regression is 75% to 80% or more.

Computerized smoking cessation program for the worksite: treatment outcome and feasibility.

This study demonstrated the effectiveness of a computer-delivered smoking cessation program for the worksite. 58 VA Medical Center employees were randomly assigned to a computer group (computerized nicotine fading and stop-smoking contest) or a contest-only group. In comparison with the contest-only group, the computer group had nonsignificantly higher abstinence rates across follow-up, had marginally lower CO levels at the 3- and 6-month follow-ups, and smoked cigarettes with lower nicotine levels at the 10-day and 6-month follow-ups.

Structure of cis-polyisoprene from Lactarius mushrooms.

Sporophores from five species of Lactarius mushrooms had a liquid rubber content of 0.1% to 7% based on the dry weight. Rubber from L. volemus, L. chrysorrheus and L. hygrophoroides was found to be a homologue of polyprenol being composed of dimethylallyl group, two trans isoprene units, 160-300 cis isoprene units, and terminal hydroxyl or ester group aligned in that order by 13C-NMR analysis. The ratio of fatty acid ester group to hydroxyl group was about 9/1 to 5/5. The number of both terminal groups and trans units decreased during aging of sporophores. Rubber from L. piperatus, L. vellereus and L. subpiperatus was found to be cis polyisoprene having very small quantities of both terminal groups and trans units. The biosynthesis of cis polyisoprene in Lactarius mushrooms was found to start from trans, trans-farnesyl pyrophosphate. The termination was assumed to occur by esterification of polyisoprenyl pyrophosphate. Occurrence of some chemical modifications on both terminal groups was presumed during aging of sporophores.

Salted fish and nasopharyngeal carcinoma in Malaysia.

The evidence for a hypothesis that eating salted fish is associated with nasopharyngeal carcinoma (NPC) is reviewed. The hypothesis was tested among Malaysian Chinese using a matched case-control design. The kinds of salted fish and patterns of use were also investigated in a control group comprising 100 Chinese, 50 Malay and 50 Indian households. During 1980, in Selangor, Malaysia, interviews with 100 Chinese cases of NPC and 100 non-disease controls indicated that salted fish consumption during childhood was a significant risk (relative risk = 3.0, P = 0.04), with an elevated risk for daily as opposed to less frequent consumption. Salted fish consumption during adolescence was a less significant risk, and current consumption not at all. There were 19 kinds of fishes reported as being eaten as salted fish by the 200 control households. There were marked differences between ethnic groups in preference for different kinds: Chinese preferred red snapper (74% of households), Malay jewfish (54%) and Indian red snapper (28%). Salted fish was hardly ever eaten daily by any household; weekly was a moderate frequency in all ethnic groups; less than weekly most common. There were no statistically significant differences between Chinese NPC case and non-disease control participants in kind of salted fish eaten. Results were the same when the data were analyzed by sex, subethnic group and income.

Molecular characterization of Sp serotype strains of infectious pancreatic necrosis virus exhibiting differences in virulence.

Infectious pancreatic necrosis virus (IPNV), a prototype virus of the family Birnaviridae, exhibits a high degree of antigenic variability, pathogenicity and virulence in salmonid species. The Genomic Segment A encodes all the structural (VP2 and VP3) and nonstructural (NS) proteins, whereas Segment B encodes the viral RNA-dependent RNA polymerase (VP1). We tested 3 different IPNV isolates (Sp103, Sp116 and Sp122) isolated during field outbreaks in Norway for their ability to cause mortality in fry and post-smolt of Atlantic salmon Salmo salar L. The cumulative mortality following experimental challenge in fry was 29% for Sp122 followed by 19% for Sp116 and 15% for Sp103. In post-smolt, the corresponding mortality rates were 79, 46 and 16%, respectively. Comparisons of the deduced amino acid sequences of Segments A and B of all 3 Sp strains revealed substitutions of residues in 13 positions, of which 6 are in VP2, 2 in VP3, and 5 in VP1. Our results suggest that these residues, especially those in the outer capsid VP2, may be involved in the virulence of IPNV. Genome Segment A of the Sp serotype is 3097 nucleotides long and contains a major open reading frame (ORF) encoding a polyprotein of 972 amino acids, which initiates at the second in-frame start codon at Position 119. This was ascertained by making mutants of Segment A clone using site-directed mutagenesis, followed by in vitro transcription-coupled translation reaction and immunoprecipitation analyses. In addition, Segment A also encodes a 15 kDa arginine-rich non-structural protein from a small ORF, preceding and partially overlapping the polyprotein ORF, which is truncated to 12 kDa in the virulent Sp122 strain. Moreover, Segment A could encode a novel, putative 25 kDa protein from another ORF between VP2 and VP4 coding regions, which is only detected in the Sp serotype. Segment B is 2777 nucleotides long and encodes in a single large ORF (a polypeptide of 844 amino acid residues), VP1.

Melanoma in childhood and adolescence: clinical and pathological features of 48 cases.

Forty-eight cases of melanoma occurring in patients under 20 years of age were reviewed from a 23-year period at a single center. Fourteen of the patients were preadolescent children and 44 were Caucasian. Histological review of 44 available primary tumors showed only superficial spreading and nodular types. Thickness ranged from 0.23 mm to 8.50 mm, with a median of 1.03 mm. Ulceration was present in 7%, necrosis in 35%, evidence of regression in 16%, and antecedent nevus in 49% of the cases. The overall 5-year survival is 77%, with a median follow-up of 48 months. There is no detectable survival difference between preadolescent children and adolescents. Several treatment failures occurred after improper biopsy and/or inaccurate original diagnosis of Spitz's nevus. Of 38 stage I and II patients given definitive surgical treatment by the authors, the 5-year survival is 90%. Although histological confusion with Spitz's nevi occasionally occurs, melanoma in this age group can be treated with good results.