Immune status and the efficacy of adjuvant radiotherapy for patients with localized Merkel cell carcinoma of the head and neck.

PURPOSE: Immunosuppressed (IS) patients are at increased risk for developing Merkel cell carcinoma (MCC) with worsened outcomes compared to immunocompetent (IC) patients. We sought to determine the effects of immune status on the efficacy of adjuvant RT regarding OS for patients with stage I, II or III (localized) MCC of the head and neck. METHODS/PATIENTS: The National Cancer Database was queried for patients with resected, localized MCC of the head and neck with known immune status. Kaplan-Meier methods were used to describe OS. Log-rank tests, multivariable Cox regression models and interaction effect testing were used to compare OS by subgroup categorized by patient and treatment factors including immune status and adjuvant RT receipt. RESULTS: A total of 892 (89.6%) IC and 104 (10.4%) IS patients with MCC of the head and neck were included. Adjuvant RT was associated with improved 3-year OS rate for both IS patients (49.4% vs. 35.5%, p = 0.0467) and stage I/II IC patients (72.4% vs. 62.9%, p = 0.0092). Adjuvant RT was associated with decreased hazard of death (HR 0.77, 95% CI 0.62-0.95). Interaction effect testing did not demonstrate a difference in the efficacy of adjuvant RT on OS between IC and IS status (p = 0.157). CONCLUSIONS: In this NCDB analysis, adjuvant RT was associated with decreased hazard of death for patients with localized MCC of the head and neck regardless of immune status and should be considered for both IS and IC patients.

Geochemical sources, forms and phases of soil contamination in an industrial city.

This study examines current soil contamination in an Australian industrial city, Newcastle. Public (roadside verges and parks) and private (homes) surface soils (n=170) contained metal(loid)s elevated above their respective Australian Health Investigation Levels (HIL). Lead (Pb), the most common contaminant in the city, exceeds the HIL for residential soils (HIL-A, 300mg/kg) in 88% of private soils (median: 1140mg/kg). In-vitro Pb bio-accessibility analysis of selected soils (n=11) using simulated gastric fluid showed a high affinity for Pb solubilisation (maximum Pb concentration: 5190mg/kg, equating to 45% Pb bio-accessibility). Highly soluble Pb-laden Fe- and Mn-oxides likely contribute to the bio-accessibility of the Pb. Public and private space surface soils contain substantially less radiogenic Pb (range: 208Pb/207Pb: 2.345-2.411, 206Pb/207Pb: 1.068-1.312) than local background soil (208Pb/207Pb: 2.489, 206Pb/207Pb: 1.198), indicating anthropogenic contamination from the less radiogenic Broken Hill type Pb ores (208Pb/207Pb: 2.319, 206Pb/207Pb: 1.044). Source apportionment using Pb isotopic ratio quantification and soil mineralogy indicate the city's historic copper and steel industries contributed the majority of the soil contaminants through atmospheric deposition and use of slag waste as fill material. High-temperature silicates and oxides combined with rounded particles in the soil are characteristic of smelter dust emissions. Additionally, a preliminary investigation of polycyclic aromatic hydrocarbons in soils, sometimes associated with ferrous metal smelting, coal processing or burning of fossil fuels, shows that these too pose a health exposure risk (calculated in comparison to benzo(a)pyrene: n=12, max: 13.5mg/kg, HIL: 3mg/kg).

Fifteen-year trends and predictors of preparation for pregnancy in women with pre-conception Type 1 and Type 2 diabetes: a population-based cohort study.

AIMS: To investigate trends in indicators of preparation for pregnancy in women with Type 1 and Type 2 diabetes and explore their predictors. METHODS: Data on 2293 pregnancies delivered during 1996-2010 by women with Type 1 (n = 1753) and Type 2 (n = 540) diabetes were obtained from the Northern Diabetes in Pregnancy Survey. Multiple logistic regression was used to analyse the relationship between potential predictors and three indicators of inadequate pregnancy preparation: non-attendance for pre-conception care; no pre-conception folate consumption; and peri-conception HbA(1c) ≥ 53 mmol/mol (≥ 7%). RESULTS: Overall, 40.3% of women with diabetes attended pre-conception care, 37.4% reported pre-conception folate consumption, and 28.2% had adequate peri-conception HbA1c . For all patients, pre-conception folate consumption improved over time, while peri-conception glucose control did not. Attendance for pre-conception care for women with Type 1 diabetes significantly declined. Residence in deprived areas, smoking and younger maternal age (for women aged < 35 years) were independently associated with all three indicators of inadequate preparation for pregnancy. Additional predictors of inadequate peri-conception HbA(1c) were: Type 1 diabetes (adjusted odds ratio 5.51, 95% CI 2.71-11.22), longer diabetes history (adjusted odds ratio 1.16, 95% CI 1.09-1.23 per year increase for those with < 15 years' diabetes duration), non-white ethnicity (adjusted odds ratio 3.13, 95% CI 1.23-7.97) and higher BMI (adjusted odds ratio 1.05, 95% CI 1.01-1.09 per 1-kg/m(2) increase). Non-attendance for pre-conception care was additionally associated with Type 2 diabetes (P = 0.003) and multiparity (P < 0.0001). CONCLUSIONS: There are socio-demographic inequalities in preparation for pregnancy among women with diabetes. Women with Type 2 diabetes were less likely to attend pre-conception care. Pre-conception services need to be designed to maximize uptake in all groups.

Improved antenatal detection of congenital anomalies in women with pre-gestational diabetes: population-based cohort study.

AIMS: To compare antenatal detection of congenital anomaly in women with and without pre-gestational diabetes and their pregnancy outcomes in a regional cohort study. METHODS: Data from a total of 7148 singleton pregnancies with a congenital anomaly delivered between 1 January 1996 and 31 December 2008 were extracted from the Northern Diabetes in Pregnancy and Northern Congenital Abnormality Surveys. Antenatal ultrasound detection rates of congenital anomaly in pregnancies complicated by major non-chromosomal congenital anomaly and resulting in live birth, stillbirth, late miscarriage (20-23 weeks of gestation) or termination of pregnancy for a congenital anomaly, were compared between women with and without diabetes (120 and 7028, respectively). RESULTS: A significantly higher rate of antenatal detection of congenital anomalies was observed in women with diabetes compared with women without diabetes (50.8 vs. 38.6%, respectively; relative risk 1.32; 95% CI 1.10-1.57; P = 0.003). Cardiovascular anomalies were the only group with a significantly higher antenatal detection rate in women with diabetes (31.8 vs. 10.4%; relative risk 3.05; 95% CI 1.95-4.76; P < 0.00001). This difference remained after excluding cases of ventricular septal defect (52.2 vs. 16.3%; relative risk 3.20; 95% CI 2.13-4.80; P < 0.0001). Among women with diabetes, male fetal sex was the only factor associated with a higher antenatal detection rate. There were no differences in the rates of termination of pregnancy, late miscarriage, stillbirth or infant death between groups. CONCLUSIONS: Antenatal detection of cardiovascular anomalies was higher in women with diabetes, suggesting that recommendations for enhanced cardiovascular scanning may improve detection. Greater awareness of the increased risk of anomalies in other organ systems is needed.

HbA(1c) and birthweight in women with pre-conception type 1 and type 2 diabetes: a population-based cohort study.

AIMS/HYPOTHESIS: To investigate clinical and sociodemographic predictors of birthweight in singletons born to women with type 1 or type 2 diabetes. METHODS: Normally formed singleton live births and intrapartum stillbirths, born to women with pre-conception diabetes during 1996-2008, were identified from the population-based Northern Diabetes in Pregnancy Survey (n = 1,505). Associations between potential predictors and birthweight were analysed by multiple regression. RESULTS: Potentially modifiable independent predictors of increase in birthweight were pre-pregnancy care (adjusted regression coefficient [b] = 87.1 g; 95% CI 12.9, 161.3), increasing third-trimester HbA(1c) ≤7% (53 mmol/mol) (b = 310.5 g per 1% [11 mmol/mol]; 95% CI 246.3, 374.7) and increasing maternal BMI (b = 9.5 g per 1 kg/m(2); 95% CI 3.5, 15.5). Smoking during pregnancy (b = -145.1 g; 95% CI -231.4, -58.8), later gestation at first antenatal visit (b = -15.0 g; 95% CI -26.9, -3.0) and higher peri-conception HbA(1c) (b = -48.2 g; 95% CI -68.8, -27.6) were independently associated with birthweight reduction. Pre-pregnancy nephropathy (b = -282.7 g; 95% CI -461.8, -103.6) and retinopathy (b = -175.5 g; 95% CI -269.9, -81.0) were independent non-modifiable predictors of reduced birthweight, while greater maternal height was a non-modifiable predictor of increasing birthweight (b = 17.8 g; 95% CI 12.3, 23.2). Other predictors of birthweight increase were male sex, multiparity and increasing gestational age at delivery. Type or duration of diabetes, socioeconomic status and ethnicity were not associated with continuous birthweight. CONCLUSIONS/INTERPRETATION: Poor glycaemic control before and throughout pregnancy is associated with abnormal fetal growth, with increasing peri-conception HbA(1c) predicting weight reduction and increasing third-trimester HbA(1c) predicting increased birthweight. Women with microvascular complications of diabetes may require increased surveillance to detect fetal growth restriction.

Impact of maternal body mass index on the antenatal detection of congenital anomalies.

OBJECTIVE: To investigate the association between maternal body mass index (BMI) and antenatal ultrasound detection of congenital anomalies. DESIGN: Population-based register study. SETTING: North of England (UK). POPULATION: All pregnancies (n = 3096) associated with a congenital anomaly notified to the Northern Congenital Abnormality Survey (NorCAS) during 2006-2009. Cases with chromosomal and teratogenic anomalies (n = 611) or without information on antenatal scanning (n = 4) were excluded. METHODS: Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for antenatal detection according to maternal BMI categories were estimated using logistic regression. MAIN OUTCOME MEASURES: For all anomalies combined, cases were defined as 'detected' if any congenital anomaly was suspected antenatally. Organ system-specific anomalies were defined as detected if an anomaly of the correct system was suspected. RESULTS: Antenatal detection of any anomaly occurred in 1146 of 2483 (46.2%) cases with normal karyotype. The odds of detection were significantly decreased in obese (BMI ≥ 30 kg/m(2)) women compared with women of recommended BMI (18.5-24.9 kg/m(2); aOR, 0.77; 95% CI, 0.60-0.99; P = 0.046). Cardiovascular system anomalies were suspected antenatally in 109 of 945 (11.5%) cases. The odds of detecting a cardiovascular anomaly were significantly greater in underweight women (BMI < 18.5 kg/m(2)) than in women of recommended BMI (aOR, 2.95; 95% CI, 1.13-7.70; P = 0.027). There was no association between BMI and detection in any other organ system or between BMI and termination of pregnancy for fetal anomaly. CONCLUSIONS: Antenatal ultrasound detection of a congenital anomaly is decreased in obese pregnant women. This has implications for the scanning and counselling of obese women.

Peri-conception hyperglycaemia and nephropathy are associated with risk of congenital anomaly in women with pre-existing diabetes: a population-based cohort study.

AIMS: The aim of this study was to quantify the risk of major congenital anomaly, and to assess the influence of peri-conception HbA(1c) and other clinical and socio-demographic factors on the risk of congenital anomaly occurrence in offspring of women with type 1 and type 2 diabetes diagnosed before pregnancy. METHODS: This was a population-based cohort study using linked data from registers of congenital anomaly and diabetes in pregnancy. A total of 401,149 singleton pregnancies (1,677 in women with diabetes) between 1996 and 2008 resulting in live birth, fetal death at ≥20 weeks' gestation or termination of pregnancy for fetal anomaly were included. RESULTS: The rate of non-chromosomal major congenital anomaly in women with diabetes was 71.6 per 1,000 pregnancies (95% CI 59.6, 84.9), a relative risk of 3.8 (95% CI 3.2, 4.5) compared with women without diabetes. There was a three- to sixfold increased risk across all common anomaly groups. In a multivariate analysis, peri-conception glycaemic control (adjusted OR [aOR] 1.3 [95% CI 1.2, 1.4] per 1% [11 mmol/mol] linear increase in HbA(1c) above 6.3% [45 mmol/mol]) and pre-existing nephropathy (aOR 2.5 [95% CI 1.1, 5.3]) were significant independent predictors of congenital anomaly. Associations with gestation at booking (aOR 1.1 [95% CI 1.0, 1.1]) and parity (aOR 1.6 [95% CI 1.0, 2. 5]) were not significant. Unadjusted risk was higher for women from deprived areas or who did not take folate. Type and duration of diabetes, ethnicity, age, BMI, preconception care, smoking and fetal sex were not associated with congenital anomaly risk. CONCLUSIONS: Peri-conception glycaemia is the most important modifiable risk factor for congenital anomaly in women with diabetes. The association with nephropathy merits further study.

Analysis of airway epithelial regeneration and repair following endobronchial brush biopsy in sheep.

Understanding the fundamental processes involved in repairing the airway wall following injury is fundamental to understanding the way in which these processes are perturbed during disease pathology. Indeed complex diseases such as asthma and chronic obstructive pulmonary disease (COPD) have at their core evidence of airway wall remodeling processes that play a crucial functional role in these diseases. The authors sought to understand the dynamic cellular events that occur during bronchial airway epithelial repair in sheep. The injury was induced by endobronchial brush biopsy (BBr), a process that causes epithelial débridement and induces a consequential repair process. In addition, the current experimental protocol allowed for the time-dependent changes in airway wall morphology to be studied both within and between animals. The initial débridement was followed by evidence of dedifferentiation in the intact epithelium at the wound margins, followed by proliferation of cells both within the epithelium and in the deeper wall structures, notably in association with the submucosal glands and smooth muscle bundles. Seven days after injury, although the airway wall was thickened at the site of damage, the epithelial layer was intact, with evidence of redifferentiation. These studies, in demonstrating broad agreement with previous studies in small animals, indicate the wider relevance of this system as a comparative model and should provide a solid basis upon which to further characterize the critical cellular and molecular interactions that underlie both effective restitution and pathological repair.

Phylogeography and molecular epidemiology of Papaya ringspot virus.

Papaya ringspot virus (PRSV) is the most important virus affecting papaya and cucurbit plants in tropical and subtropical areas. PRSV isolates are divided into biotypes P and W: both the P and W types naturally infect plants in the family Cucurbitaceae, whereas the P type naturally infects papaya (Carica papaya). Understanding the origin and nature of the PRSV genetic diversity and evolution is critical for the implementation of control strategies based on cross-protection and the deployment of transgenic plants that show resistance to virus isolates highly similar to the transgene. The molecular epidemiology of PRSV was evaluated by analyzing the nucleotide sequence of the capsid protein (CP) and helper component-proteinase (HC-Pro) genes of isolates from around the world, including newly characterized ones from Colombia and Venezuela, using a relaxed molecular clock-based approach and a phylogeographic study. Our results confirm previous estimates on the origin of PRSV around 400 years ago and suggest distinct dispersion events from the Indian Peninsula to the rest of Asia, via Thailand, and subsequently to the Americas. A historical reconstruction of the P- and W-type characters in the phylogenetic study supports the need to revise the hypothesis that PRSV-P derives from PRSV-W since our results suggest that the ancestral state could be either of the two biotypes. Moreover, estimates of epidemic growth predict an increasing genetic diversity of the virus over time that has direct implications for control strategies of PRSV based on cross-protection and the use of transgenic plants.

Maternal body mass index and the risk of fetal and infant death: a cohort study from the North of England.

BACKGROUND: Early pregnancy obesity (body mass index, BMI, ≥ 30 kg/m(2)) carries significant health implications. This cohort study investigates the association between early pregnancy BMI and the risk of fetal and infant death in pregnancies not affected by congenital anomalies or pre-gestational diabetes. METHODS: Data on singleton pregnancies delivered during 2003-2005 at five hospitals were linked with data from three regional registers: the Northern Perinatal Mortality Survey, the Northern Diabetes in Pregnancy Survey and the Northern Congenital Abnormality Survey. Logistic regression models were used to determine the crude and adjusted odds ratios (aOR) of a spontaneous fetal death (≥ 20 weeks gestation) and infant death (aged up to 1 year), among underweight (BMI <18.5 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)) and obese women compared with women of recommended BMI (18.5-24.9 kg/m(2)). RESULTS: Obese women were at significantly increased risks of both fetal death [aOR = 2.32 (95% confidence interval: 1.64-3.28), P< 0.001] and infant death [aOR = 1.97 (1.13-3.45), P= 0.02]. Continuous analyses revealed a V-shaped relationship between BMI and the risk of fetal and infant death, with a minimum risk at 23 kg/m(2), and significantly increased risk thereafter for both fetal death [aOR, per unit = 1.07 (1.05-1.10), P< 0.001] and infant death [aOR, per unit = 1.06 (1.02-1.10), P= 0.007]. No significant excess risks, however, were identified for either maternal underweight [fetal death: aOR = 0.98 (0.42-2.25), P= 0.96; infant death: aOR = 1.89 (0.73-4.88), P= 0.19] or maternal overweight [fetal death: aOR = 1.34 (0.94-1.89), P= 0.10; infant death: aOR = 1.35 (0.79-2.32), P= 0.27] as categories. Except for higher rates of pre-eclampsia among stillbirths, no specific cause of death could explain the increased odds of fetal and infant death among the obese. CONCLUSIONS: Early pregnancy obesity is significantly associated with fetal and infant death, independent of the known relationships with congenital anomalies and maternal pre-gestational diabetes.

Pre-clinical evaluation of three non-viral gene transfer agents for cystic fibrosis after aerosol delivery to the ovine lung.

We use both large and small animal models in our pre-clinical evaluation of gene transfer agents (GTAs) for cystic fibrosis (CF) gene therapy. Here, we report the use of a large animal model to assess three non-viral GTAs: 25 kDa-branched polyethyleneimine (PEI), the cationic liposome (GL67A) and compacted DNA nanoparticle formulated with polyethylene glycol-substituted lysine 30-mer. GTAs complexed with plasmids expressing human cystic fibrosis transmembrane conductance regulator (CFTR) complementary DNA were administered to the sheep lung (n=8 per group) by aerosol. All GTAs gave evidence of gene transfer and expression 1 day after treatment. Vector-derived mRNA was expressed in lung tissues, including epithelial cell-enriched bronchial brushing samples, with median group values reaching 1-10% of endogenous CFTR mRNA levels. GL67A gave the highest levels of expression. Human CFTR protein was detected in small airway epithelial cells in some animals treated with GL67A (two out of eight) and PEI (one out of eight). Bronchoalveolar lavage neutrophilia, lung histology and elevated serum haptoglobin levels indicated that gene delivery was associated with mild local and systemic inflammation. Our conclusion was that GL67A was the best non-viral GTA currently available for aerosol delivery to the sheep lung, led to the selection of GL67A as our lead GTA for clinical trials in CF patients.

Validation of recombinant Sendai virus in a non-natural host model.

We have previously shown that recombinant Sendai virus (SeV) vector, derived from murine parainfluenza virus, is one of the most efficient vectors for airway gene transfer. We have also shown that SeV-mediated transfection on second administration, although reduced by 60% when compared with levels achieved after a single dose, is still high because of the efficient transfection achieved by SeV vector in murine airways. Here, we show that these levels further decrease on subsequent doses. In addition, we validated SeV vector repeat administration in a non-natural host model, the sheep. As part of these studies we first assessed viral stability in a Pari LC Plus nebuliser, a polyethylene catheter (PEC) and the Trudell AeroProbe. We also compared the distribution of gene expression after PEC and Trudell AeroProbe administration and quantified virus shedding after sheep transduction. In addition, we show that bronchial brushings and biopsies, collected in anaesthetized sheep, can be used to assess SeV-mediated gene expression over time. Similar to mice, gene expression in sheep was transient and had returned to baseline values by day 14. In conclusion, the SeV vector should be strongly considered for lung-related applications requiring a single administration of the vector even though it might not be suitable for diseases requiring repeat administration.

Maternal body mass index and congenital anomaly risk: a cohort study.

OBJECTIVE: To investigate the association between maternal body mass index (BMI) and major, structural congenital anomalies. DESIGN: Cohort study using prospectively collected data. METHODS: Data on all singleton pregnancies booked at five maternity units in the north of England between 01 January 2003 and 31 December 2005 and data on congenital anomalies notified to the Northern Congenital Abnormality Survey were linked using key variables. Maternal pre-gestational diabetic status was derived from the Northern Diabetes in Pregnancy Survey. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated by maximum-likelihood logistic regression models, with missing values modelled as explicit categories. RESULTS: There was a total of 41,013 singleton pregnancies during the study period, of which 682 were affected by a structural congenital anomaly, a total prevalence of 166 (95% CI: 154, 179) per 10,000 registered births. Overall, the risk of a congenital anomaly was significantly increased among the maternal underweight (BMI

Streptococcal protective antigens (Spa): a new family of type-specific proteins of group A streptococci.

Previous studies in our laboratory described a new group A streptococcal protective antigen (Spa) in type 18 streptococci that was distinct from the type 18 M protein. This study was undertaken to identify additional serotypes of group A streptococci that express Spa proteins. PCR techniques were used to identify and clone a new spa gene from type 36 streptococci. The 5' sequence of spa36 was highly variable compared to spa18, while the 3' sequence was conserved. Antisera against Spa36 opsonized type 36 streptococci but not type 18 streptococci, indicating that the opsonic Spa epitopes were type-specific. Antisera against the conserved carboxy-terminal half of Spa18 were used to identify Spa or Spa-like proteins expressed on the surface of 25 of 70 different serotypes of GAS. Spa proteins may represent a new family of type-specific surface antigens that function in concert with M proteins to elicit protective immune responses.

Lifecourse predictors of adult respiratory function: results from the Newcastle Thousand Families Study.

BACKGROUND: Impaired development in utero is suggested to increase the risk of poor respiratory health in adulthood, although a consensus has not been reached. A possible explanation for discrepancies between previous studies is inconsistent controlling for potential confounding factors, particularly childhood infections. Also, little is known regarding the relative importance of factors operating at different stages of the lifecourse. We have used detailed longitudinal data from the Newcastle Thousand Families cohort to assess the impact of birth weight, and various other factors acting throughout the lifecourse, on predicting forced expiratory volume in 1 s (FEV(1)). METHODS: Detailed information was collected prospectively during childhood, including birth weight, childhood infections and socioeconomic circumstances. At age 49-51 years, 412 study members attended for clinical examination and measurement of FEV(1). These data were analysed in relation to a range of factors from across the lifecourse using linear regression models. RESULTS: After adjustment for all other significant variables, increasing birth weight, standardised for sex and gestational age (p = 0.011), being breast fed for more than 4 weeks (p = 0.017), less frequent childhood lower respiratory tract infections (LRTI) (p = 0.015), non- smoking (p<0.001), lower body fat percentage (p = 0.010), male sex (p<0.001), no history of asthma (p = 0.013) and greater adult height (p<0.001) were all independently associated with higher adult FEV(1). CONCLUSION: Adult lung function is influenced by numerous factors during an individual's lifetime, acting both directly and indirectly throughout the lifecourse. As expected, sex, height and smoking were the most important predictors of FEV(1), but birth weight, breast feeding and childhood LRTIs also contributed significantly.

Varying genetic diversity of Papaya ringspot virus isolates from two time-separated outbreaks in Jamaica and Venezuela.

Coat protein sequences of 22 Papaya ringspot virus isolates collected from different locations in Jamaica and Venezuela in 1999 and 2004, respectively, were determined and compared with sequences of isolates from earlier epidemics in 1990 and 1993. Jamaican isolates collected in 1999 exhibited nucleotide sequence identities between 98 and 100% but shared lower identities of 92.2% with an isolate collected in 1990. Isolates from the 2004 epidemic in Venezuela exhibited more heterogeneity, with identities between 88.7 and 98.8%. However, isolates collected in 1993 were more closely related (97.7%). The viral populations of the two countries are genetically different and appear to be changing at different rates; presumably driven by introductions, movement of plant materials, geographical isolation, and disease management practices.

Momordica charantia is a Weed Host Reservoir for Papaya ringspot virus Type P in Jamaica.

Papaya rinsgpot virus type P (PRSV), a member of the genus Potyvirus in the family Potyviridae, is primarily transmitted by aphids in a nonpersistent manner (2). The virus is geographically widespread but has a narrow host range within the plant families Caricaceae, Chenopodiaceae, and Cucurbitaceae (2). The first reported epidemic of PRSV in Jamaica was during the late 1980s (1). Since then, the virus has spread across the island and is recognized as a potential problem for continued production of papaya (Carica papaya L.). In the summers of 1999 and 2000, prominent vein clearing symptoms were observed on leaves of a common weed, cerasee (Momordica charantia L.), in papaya orchards of western Jamaica. This weed, a climbing annual in the Cucurbitaceae family used in a variety of local herbal preparations, was found to be growing on fences or the ground along the periphery of the orchards. Leaf samples were collected and tested for PRSV by double-antibody sandwich (DAS)-ELISA with polyclonal antibodies (Agdia Inc, Elkhart, IN). In addition, crude sap extracts from 12 cerasee leaf samples that were diluted 1:20 were mechanically inoculated onto six plants each of cerasee and papaya. Within 2 weeks, vein clearing symptoms were observed on cerasee and symptoms (vein clearing followed by mosaic development and leaf distortions) typical of PRSV infection were obtained on papaya (2). All original leaf samples and inoculated plants tested positive in DAS-ELISA. In subsequent vector transmission tests, 10 healthy cerasee or papaya seedlings were inoculated with aphids (Aphis gossypii) that were previously permitted to feed on PRSV-infected papaya or cerasee. High rates of virus transmission were achieved in three tests from cerasee to papaya (77 to 83%), papaya to cerasee (90 to 93%), and cerasee to cerasee (60 to 70%). Total RNA from papaya samples was subjected to reverse transcriptase-PCR using primers to the capsid protein gene (3). A single fragment of the expected size (approximately 996 bp) was amplified and sequenced and showed high nucleotide identity (90.3 to 91.4%) with previously reported PRSV type P from Jamaica (GenBank Accession No. DQ104823), Cuba (GenBank Accession No. DQ089482), Florida (GenBank Accession No. AF196839), Brazil (GenBank Accession No. AF344650), and Hawaii (GenBank Accession No. S46722). To our knowledge, this is the first report of the natural occurrence of PRSV on a weed host in Jamaica. Because of its widespread distribution and potential of serving as a reservoir of PRSV, cerasee may play a role in the epidemiology of PRSV. References: (1) M. Chin et al. Jam. J. Sci. Technol. 14:58, 2003. (2) D. Purcifull et al. No 292 in: Descriptions of Plant Viruses. CMI/AAB, Surrey, England, 1984. (3) J. Slightom. Gene 100:251, 1991.

Alterations of microsomal monooxygenase system and carcinogen metabolism by streptozotocin-induced diabetes in rats.

The effects of diabetes on the liver microsomal monooxygenase enzymes and carcinogen metabolism have been studied in rats. Treatment with streptozotocin causes a marked enhancement in microsomal N-nitrosodimethylamine (NDMA) demethylase activity. The enhancement is due mainly to the induction of a high affinity NDMA demethylase (Km, approximately 0.05 mM) which is accompanied by the induction of a protein species with mol. wt. of 50,000. The treatment also induces aniline hydroxylase whose activity is in parallel with NDMA demethylase. Streptozotocin-induced diabetes also increases the metabolism of N-nitrosomethylethylamine but not that of N-nitrosomethylaniline or N-nitrosomethylbenzylamine. On the other hand, diabetes decreases the metabolism of benzo[a]pyrene, benzphetamine, and ethylmorphine. The result suggest that diabetes causes an alteration of the composition of cytochrome P-450 isozymes; the forms efficient in metabolizing NDMA are increased while certain other forms of cytochrome P-450 are decreased.