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PubMed2003

Functional p53 increases prostate cancer cell survival after exposure to fractionated doses of ionizing radiation.

External beam radiation therapy is an effective therapy for localized prostate cancer, although failures occur at high rates. One variable that may affect the radiosensitivity of prostate tumor cells is their p53 status because this gene controls radiation-induced cell cycle arrest, apoptosis, and the repair of DNA damage. Using a system in which p53 function was conditionally restored to p53-null PC3 prostate cancer cells by stable transfection with a human temperature-sensitive p53 mutant allele, we tested the hypothesis that functional p53 increases cell cycle arrest and contributes to increased clonogenic survival after ionizing radiation (IR) of prostate carcinoma cells. Cell cycle arrest and clonogenic survival in response to single and multiple daily exposures to clinically relevant 2-Gy doses of IR were examined. Whereas the temperature-sensitive p53 protein was activated by phosphorylation after IR exposure at both the restrictive and permissive temperatures, Cdkn1/p21 was only induced by functional p53 (at the permissive temperature). In the presence of functional p53, the maintenance of G(2) arrest was significantly longer (P < 0.01), and a small increase in cell survival measured by clonogenic assay was seen after exposure to a single 2-Gy dose of IR. However, functional p53 significantly increased clonogenic survival (P < 0.01) after exposure to daily doses of 2 Gy of IR and contributed to a more sustained G(2) arrest and increased G(1) arrest in response to the multifraction regimen. These studies implicate the presence of wild-type p53 with increased survival of prostate carcinoma cells after fractionated exposure to radiation. Additionally, the data provide evidence that wild-type p53 in prostate tumor cells may reduce the effectiveness of radiation therapy.

Cell Line, Tumor↗

PubMed2005

Studying toxicants as single chemicals: does this strategy adequately identify neurotoxic risk?

Despite the fact that virtually all chemicals exposure of humans are to mixtures, and that these mixed exposures occur in the context of numerous other risk modifiers, our current understanding of human health risks is based almost entirely on the evaluation of chemicals studied in isolation. This paper describes findings from our collaborative studies that prompt questions about these approaches in the context of neurotoxicology. The first section describes studies investigating the interactions of maternal Pb exposure with maternal stress. Examined across a range of outcome measures, it shows that maternal Pb can modulate the effects of maternal stress, and, conversely, stress modifies the effects of Pb. Further, effects of Pb+stress could be detected in the absence of an effect of either risk factor alone, and, moreover, the profile of effects of Pb alone differs notably from that of Pb+stress. Collectively, interactions were not systematic, but differed by brain region, gender and outcome measure. A second section describes outcomes of studies examining combined exposures to the pesticides paraquat (PQ) and maneb (MB) during development which likewise reveal potentiated effects of combined exposures. They also demonstrate examples of both progressive and cumulative neurotoxicity, including a marked vulnerability following gestational exposure to MB, to the effects of PQ, a pesticide with no structural relationship to MB. The ability of current hazard identification and risk assessment approaches to adequately identify and encompass such effects remains an important unanswered question. One consideration proposed for further evaluating potential interactions that may be of significance for the nervous system is based on a multi-hit hypothesis. It hypothesizes that the brain may readily compensate for the effects of an individual chemical itself acting on a particular target system, but when multiple target or functional sites within that one system are attacked by different mechanisms (i.e., multiple chemical exposures or chemical exposures combined with other risk factors), homeostatic capabilities may be restricted, thereby leading to sustained or cumulative damage.

Animals↗

PubMed2002

In vivo NMR microscopy allows short-term serial assessment of multiple skeletal implications of corticosteroid exposure.

Corticosteroids are in widespread clinical use but are known to have adverse skeletal side effects. Moreover, it is not known how soon these effects become apparent. Here, we describe a longitudinal approach to evaluate the short-term implications of excess corticosteroid exposure by quantitative in vivo magnetic resonance imaging and spectroscopy in conjunction with digital image processing and analysis in a rabbit model. Two-week treatment with dexamethasone induced a significant reduction in trabecular bone volume, which occurred at the expense of uniform trabecular thinning without affecting network architecture. Paralleling the loss in bone volume was conversion of hematopoietic to yellow marrow in the femoral metaphysis and atrophy of the femoral epiphyseal growth plate. This work demonstrates that detailed quantitative morphometric and physiological information can be obtained noninvasively at multiple skeletal locations. The method is likely to eventually replace invasive histomorphometry in that it obviates the need to sacrifice groups of animals at multiple time points. Finally, this work, which was performed on a clinical scanner, has implications for evaluating patients on high-dose steroid treatment.

Animals↗

PubMed2006

The association between demolition activity and children's blood lead levels.

Urban renewal efforts are a priority for many American cities. As efforts to reconstitute urban centers increase, the demolition of old, deteriorated structures has accelerated. Recent studies have identified demolitions as a potential source of environmental lead exposure. We conducted a study examining the relationship between demolition activity and blood lead levels of children residing in neighborhoods where demolition activity occurred. A retrospective cohort study was conducted in St. Louis City, Missouri. The study period was January 1, 2002 to December 31, 2002. Data were obtained from the Missouri Childhood Lead Poisoning Prevention Program's (CLPPP) lead surveillance system and St. Louis Demolition Permit Database. Children were considered exposed to a demolition if they had a blood lead test within 45 days of any demolition on a census block. Exposure was classified as both a dichotomous (yes/no) and a categorical (none/one/multiple) variable and was analyzed separately. Linear regression models were developed to determine effects of demolitions on blood lead levels. A total of 1196 children 6-72 months of age living in 395 census blocks were included. 314 (26.3%) were exposed and 882 (73.7%) were unexposed to a demolition. In an adjusted model, exposure to multiple demolitions was found to have significant effects on children blood lead levels (coefficient=0.281; 95% CI=0.069, 0.493; P-value=0.010). Age of the child, race, and age of housing where children's resided were also significant predictors. This study suggests that multiple demolitions within a census block may significantly increase children's blood lead levels. The findings may be useful to municipal planners in older cities where demolitions are being used as an urban renewal tool.

Child, Preschool↗

PubMed2003

Hepatitis C virus: prevalence and routes of infection among blood donors of West Mexico.

In Latin America few studies have explored frequency and risk factors predicting hepatitis C virus (HCV) infection in blood donors. In this study we determined the prevalence of HCV infection in blood donors from West Mexico. Potential risk factors, clinical, histological and virologic characteristics presented in this group were also evaluated. METHODS: HCV antibodies were evaluated in 57108 blood donors with commercial second-generation enzyme immunoassays. Positive results were confirmed by a recombinant immunoblot assay. Repeatedly seropositive donors were further studied for risk factors, history for hepatitis, hepatic enzymes (aspartate aminotransferase and alanine aminotransferase (AST and ALT)), liver histology and hepatitis C virus-ribonucleic acid (HCV-RNA) detection. RESULTS: A total of 499 blood donors were initially tested positive doubtful for antibodies to HCV Ab (0.8%). While there was no difference in HCV prevalence with respect to age or gender, the most frequent risk factors identified were transfusion (42%), household exposure (14.8%), multiple sex partner (6.8%) and intranasal cocaine use (2.3%). Also, we found that from a subgroup of donors tested for histological analysis, 19% presented abnormal ALT levels and 90% showed abnormal liver histology. No correlation was found between abnormal ALT levels and the presence of HCV-RNA in serum. CONCLUSION: These results demonstrate a low prevalence (0.8%) of HCV infection among Western Mexican blood donors, which was comparable to those established for Western countries, but in contrast in our study the most frequent risk factor continues being transfusion followed by household exposure.

Journal Article↗

PubMed2000

Educating health professionals: a hepatitis C educational program in a health maintenance organization.

OBJECTIVE: To describe the components of and staff reaction to an educational outreach program about hepatitis C (HCV) at a managed care organization in Minnesota. PROJECT PROTOCOL: Educational programs for primary care clinicians consisted of lunch-and-learn sessions conducted in 2 phases. In phase 1 (1997-1998), educational programs were offered in 4 clinics; in phase 2 (1999), these programs were offered to a larger number of clinics. There was a structured, 2-stage recruitment process, and the protocol included multiple contacts that involved sending educational materials to participants several weeks before the program. A development team, comprised of key health maintenance organization (HMO) stakeholders, provided consultation. EVALUATION: The initiative reached more than 1000 healthcare professionals, including 150 physicians. The educational programs received very high ratings, and pre- and posttests documented significant improvement in knowledge about HCV. CONCLUSIONS: This successful educational initiative had 5 key elements: (1) value to healthcare staff (i.e., importance of the topic and quality of the programs); (2) incentives (i.e., convenience, free lunch, and continuing medical education/continuing education unit credits); (3) repeated exposures (i.e., multiple opportunities for learning, both oral and written); (4) commitment by key stakeholders at the HMO and the clinics; and (5) an exceptionally well-organized implementation plan.

Attitude of Health Personnel↗

PubMed1998

Difficulties in assessing the relationship between passive smoking and lung cancer.

Since 1981, numerous epidemiological studies have investigated the relationship between passive smoking and lung cancer in nonsmokers. The overall evidence, predominantly relating to women, indicates a weak association with the husband's smoking and many reviewers have concluded that this demonstrates a causal effect of exposure to environmental tobacco smoke (ETS). Interpreting weak associations is notoriously difficult, however, and this paper reviews problems specific to the ETS-lung cancer relationship. After describing how to select relevant studies and appropriate data, the methods for combining evidence together ('meta-analysis') are discussed, and the need to investigate sources of heterogeneity is emphasized. Separate consideration is given to various forms of bias that may affect overall relative risk estimates, including misclassification of active smoking status, confounding, systematic case-control differences, recall bias, diagnostic bias and publication bias. Sections on dose-response, multiple ETS exposure sources and other issues follow. The problems are illustrated from the available literature. It is shown there is no significant association of lung cancer with workplace, childhood or social ETS exposure or with smoking by the wife. Though statistically significant, the association with husband's smoking is weak and heterogeneous and varies widely according to various study characteristics. The association is markedly weakened by the adjustment for smoking misclassification bias and is likely to be affected by confounding and other sources of bias. While the precise extent of all the biases remains unclear, it seems impossible to conclude with any certainty that ETS causes lung cancer.

Adult↗

PubMed1996

Evaluation of lethality estimates for combustion gases in military scenarios.

To meet the military objective of determining criteria for incapacitation and lethality from toxic gas exposures, a series of small animal tests and data analyses were conducted. Carbon monoxide (CO), a narcotic gas and nitrogen dioxide (NO2), an irritant gas, along with carbon dioxide (CO2) were tested individually and in the following mixtures: (CO + CO2), (NO2 + CO2) and (NO2 + CO + CO2). A group of six animals was exposed to each of the gases and their combinations, lethality and biophysical data were collected. We conclude that our observations of lethality from single toxic gases can be correlated with a fractional effective dose (FED) description, in which external concentrations are corrected for minute volume changes. Multiple gas exposures clearly demonstrate synergistic effects because lethality rates greatly exceed those expected from statistically independent causes. Simple addition of the FED values, however, overstates the effect and implies a competition between the narcotic and irritant gas effects. The N-Gas model, while being an additive FED model, does not appear to be in a form that could guide the setting of military exposure standards.

Animals↗

PubMed2001

Oestrogenic and antiandrogenic chemicals in the environment: effects on male reproductive health.

Exposures of human populations to pesticides and industrial pollutants, and to synthetic chemicals present in foods, beverages, and plastics, have raised concern that these substances can interfere with endogenous sex hormone function. Interference with sex hormone action can, in turn, result in a variety of developmental and reproductive anomalies. Compounds in this class are thus referred to as endocrine disruptors (EDs). EDs that affect reproductive processes in vertebrates act primarily by altering oestrogenic and antiandrogenic activities. The recent cloning of a second oestrogen receptor (ER) subtype (ERbeta) and its widespread tissue distribution pattern indicates that the first ER to be cloned, ERalpha, may not be the only, or even the primary, mediator of oestrogen action. It is anticipated that this discovery will lead to development of antagonist compounds specific to either ER subtype, and help to determine the function of each receptor subtype in reproductive and other tissues. Growing evidence suggests that EDs interfere with reproductive function at low exposure levels and cause distinct effects at different concentrations within the same organ. Developing organisms have increased susceptibility to the actions of EDs because differentiating tissues are more vulnerable to changes in hormonal milieu. Thus, children are at greater risk of toxicant-related illnesses than adults. However, most data are collected from laboratory studies, and it remains to be determined that the levels of chemicals in the environment can impair human reproductive health. There is also significant genetic variability between human and animal species in their reactions to chemicals. The effects of low-dose, chronic, and multiple chemical exposures warrant further investigation in order to characterize the risk of environmental agents to humans. The aims of this review, which will focus on male reproduction, are to: 1) identify synthetic chemicals in the environment that fall into the ED class; 2) describe their mechanisms of toxicity in reproductive tissues; and, 3) outline the direction of future research efforts with respect to EDs.

Androgens↗

PubMed2006

Predicting respiratory syncytial virus hospitalisation in Australian children.

BACKGROUND: There is limited information on respiratory syncytial virus infections among Australians, particularly those of Indigenous descent. AIM: This study identifies groups of infants at risk of hospitalisation with respiratory syncytial virus-positive lower respiratory tract infection who may be targeted for prevention with palivizumab. METHODS: Case control study: the case notes of 271 children with cases of respiratory syncytial virus-positive lower respiratory tract infection admitted to The Townsville Hospital were studied for risk factors. Controls were chosen randomly from babies born in The Townsville Hospital during that period. Multiple logistic regression analysis and classification and regression tree analysis were used to identify risk factors. RESULTS: Multiple logistic regression analysis identified birthweight <2500 g, maternal parity and marital status to be independent predictors of hospitalisation with respiratory syncytial virus-positive lower respiratory tract infection. Classification and regression tree analysis identified babies born weighing <2500 g who possessed older siblings to be at highest risk. Single mothers and smoking were additional risk factors. Indigenous babies were significantly more likely to be exposed to all of the identified risk factors. CONCLUSION: Babies born weighing <2500 g (especially with siblings) could be targeted for prevention. All Indigenous babies should be considered at high risk because of their exposure to multiple risk factors.

Adult↗

PubMed2003

Population level assessment of the family risk factors related to the onset or persistence of children's mental health problems.

BACKGROUND: Despite their great potential to inform intervention planning, screening instruments that assess children's exposure to multiple, non-behavioural risk factors are rare. The Family Risk Factor Checklist-Parent (FRFC-P), was designed to facilitate community risk factor profiling and subsequent intervention planning. The aims of the current study were to establish the psychometric properties of the FRFC-P and to examine the relative importance of family risk factors in relation to the onset versus persistence of children's mental health problems. METHOD: Data were collected from 1022 parents of 4-8-year-old children as part of the Promoting Adjustment in Schools Project (PROMAS). The FRFC-P assessed children's exposure to risk across five domains: adverse life events and instability (ALI); family structure and SES (SES); parenting practices (PAR); parental verbal conflict and mood problems (VCM); and parental antisocial and psychotic behaviour (APB). RESULTS: The FRFC-P had satisfactory test-retest reliability and construct validity, but modest internal consistency. Risk assessed by the PAR domain was the most important determinant of mental health problem onset, while the PAR, VCM, and APB domains were the strongest predictors of mental health problem persistence. CONCLUSIONS: These findings highlight the importance of considering risk factors for onset separately from risk factors for persistence of mental health problems and indicate that the studied population may benefit the most from preventive interventions that address parenting practices and treatment interventions that address parenting practices, and parental mood problems, conflict, antisocial behaviour, and psychiatric disorders.

Child↗

PubMed1996

Occupational Exposures and Risks of Spontaneous Abortion among Female Veterinarians.

Associations between occupational exposures and spontaneous abortion (SA) in a cohort of female veterinarians were studied with pregnancy and job-exposure history data collected as part of a mixed-mode survey of all women graduating from U.S. veterinary colleges during the 11-year period 1970-1980 (N = 2,997; response rate 85.0%). Data analysis focused on SA risks among postgraduation pregnancies in relation to 1) type of clinical practice at the time of conception and 2) self-reported occupational exposures to 13 exposure entities. Multiple logistic regression was used to control for the potentially confounding effects of maternal age, gravidity, previous SA, and smoking and drinking behaviors. Pregnancies reported by veterinarians employed in all-equine practices were at highest relative risk of spontaneous abortion when compared with pregnancies reported by unemployed veterinarians [confounder-adjusted odds ratio (aOR) = 2.1; 95% confidence interval (CI), 0.6-7.4]. Agent-specific relative risk estimates ranged from 0.7 to 1.1, suggesting little or no excess risk. However, when analyses were restricted to small-animal practitioners, there was a weak association between SA risk and job-related exposure to ionizing radiation (aOR equals; 1.3; 95% CI, 0.8-2.0), a finding not inconsistent with the results of two other studies of female veterinarians. Although this study showed no strong associations, the results suggest a relationship between SA among female veterinarians and certain exposure types, and thus focus attention on other workers who encounter similar on-the-job hazards.

Journal Article↗

PubMed2006

Skeletal muscle glucose transporter protein responses to antenatal glucocorticoids in the ovine fetus.

We investigated the effects of maternal antenatal dexamethasone (Dex) treatment given as a single course (4 doses) or multiple courses (20 doses) on fetal skeletal muscle glucose transporter (GLUT) protein concentrations at 70% of gestation (106 to 107 days with term being 145 to 150 days) in the ovine fetus. Antenatal corticosteroid administration was associated with a decrease in endogenous fetal plasma cortisol concentrations (P < 0.05), fetal hyperglycemia (P < 0.02) and hyperinsulinemia (P < 0.05). These metabolic/hormonal changes were associated with a decrease in fetal body weight (P < 0.05) in the multiple course Dex group compared with the multiple course placebo group. These perturbations were associated with an increase in fetal skeletal muscle GLUT 1 concentrations that mediate basal glucose transport in the extensor digitorum lateralis and extensor digitorum longus muscles (P < 0.05) 18 h after the last dose of Dex was given in the single course group. However, in the multiple course Dex group, a small increase in GLUT 1 was observed only in the biceps femoris. In contrast, both single and multiple courses of antenatal Dex were associated with an increase in the extensor digitorum lateralis and biceps femoris muscle GLUT 4 (insulin-responsive) concentrations (P < 0.05). We conclude that antenatal corticosteroids perturb fetal glucose/insulin homeostasis, which is associated with increases in fetal skeletal muscle glucose transporters to compensate for and attenuate the associated catabolic fetal state. These changes consist of an increase in proteins that mediate basal glucose transport (GLUT 1) to meet immediate energy requirements of the fetal skeletal muscle with an increase in basal insulin sensitivity (GLUT 4) to compensate for the Dex-induced catabolic state after exposure to multiple courses of Dex.

Animals↗

PubMed2005

Spatial and management factors associated with exposure of smallholder dairy cattle in Tanzania to tick-borne pathogens.

A cross-sectional study of serum antibody responses of cattle to tick-borne pathogens (Theileria parva, Theileria mutans,Anaplasma marginale, Babesia bigemina and Babesia bovis) was conducted on smallholder dairy farms in Tanga and Iringa Regions of Tanzania. Seroprevalence was highest for T. parva (48% in Iringa and 23% in Tanga) and B. bigemina (43% in Iringa and 27% in Tanga) and lowest for B. bovis (12% in Iringa and 6% in Tanga). We use spatial and non-spatial models, fitted using classical and Bayesian methods, to explore risk factors associated with seroprevalence. These include both fixed effects (age, grazing history and breeding status) and random effects (farm and local spatial effects). In both regions, seroprevalence for all tick-borne pathogens increased significantly with age. Animals pasture grazed in the 3 months prior to the start of the sampling period were significantly more likely to be seropositive for Theileria spp. and Babesia spp. Pasture grazed animals were more likely to be seropositive than zero-grazed animals for A. marginale, but the relationship was weaker than that observed for the other four pathogens. This study did not detect any significant differences in seroprevalence associated with other management-related variables, including the method or frequency of acaricide application. After adjusting for age, there was weak evidence of localised (<5 km) spatial correlation in exposure to some of the tick borne diseases. However, this was small compared with the 'farm-effect', suggesting that risk factors specific to the farm were more important than those common to the local neighbourhood. Many animals were seropositive for more than one pathogen and the correlation between exposure to the different pathogens remained after adjusting for the identified risk factors. Identifying the determinants of exposure to multiple tick-borne pathogens and characterizing local variation in risk will assist in the development of more effective control strategies for smallholder dairy farms.

Anaplasma marginale↗

PubMed2004

Plasma sex steroid concentrations and gonadal aromatase activities in African clawed frogs (Xenopus laevis) from South Africa.

Adult African clawed frogs (Xenopus laevis) were collected from a corn-growing region (CGR) and a non-corn-growing region (NCGR) with different exposure profiles for atrazine and related triazines. Physical, chemical, and biological parameters from the catchment areas were also measured. Frogs were surveyed for possible effects of exposure to triazine herbicides on plasma testosterone (T) and estradiol (E2) titers, gonadal aromatase activity, and gonad growth (GSI). Concentrations of both T and E2 varied among locations and were correlated to some accessory factors, such as pH, several ions, and metals. Greatest median plasma T concentrations (males: 19 ng/ml; females: 16 ng/ml) occurred in frogs inhabiting NCGR as compared to those from the CGR (males: 4 ng/ml; females: 1 ng/ml). Median E2 concentrations were also greater in frogs collected from the NCGR (males: 3 ng/ml; females: 28 ng/ml) than those in frogs from the CGR (males: 2 ng/ml; females: 5 ng/ml). Because some exposure to agricultural chemicals at both regions occurred, as did simultaneous exposures to multiple chemicals, a regression analysis was employed. Negative correlations were observed between plasma T concentrations and concentrations of atrazine, deisopropylatrazine, deethylatrazine, and tertbuthylazine in females and between T and diaminochlorotriazine in males. Estradiol in females exhibited a significant negative correlation with atrazine and deethylatrazine. No correlations were observed between gonadal aromatase activity or GSI and any of the agricultural chemicals measured. Median aromatase activities in ovaries varied among sampling sites ranging from 7 to >3000 times greater than those in males when measurable. Testicular aromatase activity was below the detection limit of the assay in male frogs at most of the sites. Although exposure to agricultural inputs did not affect aromatase activities, effects of atrazine or coapplied pesticides on sex steroid homeostasis cannot be excluded at this point.

Agriculture↗

PubMed1982

Effects of multiple, chronic and early hashish exposure on mating behavior, nest-building and gestation in mice.

1. The effects of hashish extract on social behavior were investigated in pairs of mice living together from mating to parturition. The drug was administered orally to both animals at a dose of 20 mg delta 9-tetrahydrocannabinol/kg three times a week, either (I) during the 3 weeks from mating to parturition, (II) during the 12 weeks from weaning to mating and parturition, or (III) only during the 3 weeks after weaning. 2. In the mating tests, an acute administration (I) caused a general sedation. Chronically treated animals (II) showed decreased sexual behavior and lower social investigations despite significantly more non-social activities. Early drug treatment (III) had no effect on mating behavior. In all three series of experiments the females had conceived by the next morning. 3. The nest-building behavior during pregnancy was suppressed after multiple (I) and chronic (II) drug administration. In early drug-treated animals (III) the transport of nesting material was only slowed down. Non-social activities were normal or increased in all three series. 4. Parturition was significantly delayed by one day after multiple (I) and chronic (II) drug administration. The birth weight was not affected, but the litter size was decreased after chronic drug treatment. Early drug administration (III) had no effects on these parameters. 5. In conclusion, whereas tolerance to the sedative effects of hashish developed very rapidly, the drug influences on social behavior were stable. Therefore, discussions on legalization of cannabis should pay attention to the drug effects on social behavior.

Animals↗

PubMed1993

[ALAT and viral RNA as risk factors in 68 blood donors with anti-hepatitis C antibodies].

AIM: Determine the risk factors in blood donors with anti hepatitis C antibodies (anti-HCV ab) possible liver involvement and evaluation of their infectious potential by a search for viral RNA in blood. METHODS: Between July 1990 and October 1991, 19,632 blood donors were screened for hepatitis C. Antibodies to HCV were detected in 74 donors (2nd generation ELISA, Abbott). We evaluated the risk factors, determined ALAT levels and looked for circulating RNA virus by amplification of the non-coding region of the viral genome (RTPCR) in 68 of these 74 donors screened. A control was chosen arbitrarily from 103 donors with high ALAT levels, but with no antibodies to HCV nor detectable circulating viral DNA. RESULTS: The prevalence of anti-HCV ab in blood donors in 0.37%. No risk factor was found in 29 donors (43%). Parenteral exposure (former i.v. drug addiction and history of transfusions) was found to be the mode of transmission of hepatitis C in 23 donors (34%). History of NANB jaundice (non-post transfusion) was reported in 1 donor (1%). The remaining 15 donors (22%) were found to have minor risk factors - either isolated or in combination (exposure, tatoos, multiple sexual partners). Former i.v. drug addiction (p = 0.0000006) as well as a history of transfusions (p = 0.0071) are significantly more frequent in the group of donors with antibodies to HCV. None of the 35 sexual partners of the tested donors proved to be positive. 21 donors (30%) had high ALAT (+2 SD). Viral RNA was detected in blood of 26 donors (38%). The proportion of cases with positive viral RNA was 61% if only those donors with high ALAT levels were taken into consideration (13 positive of 21). CONCLUSIONS: Risk factors were found in 39 donors (57%) with antibodies to HCV. History of parenteral exposure was found to be significantly more frequent than in the control group (p = 0.0000054). Sexual transmission within couples was not demonstrated in the population tested. A positive PCR test is a probable indicator of a continuous viral replication and reflects a possible chronic hepatic involvement as well as a potential infectivity. This test is positive in at least 38% of donors with antibodies to HCV and in more than 60% of those who, in addition, have high ALAT levels.

Alanine Transaminase↗

PubMed1998

Recombination involving interstitial telomere repeat-like sequences promotes chromosomal instability in Chinese hamster cells.

The physical termini of mammalian chromosomes are capped with tandem repeats of the telomere sequence (TTAGGG)n. After fluorescence in situ hybridization with a labeled (TTAGGG)n probe, telomere-repeat-like sequences are seen as discrete bands at distinct intrachromosomal sites in a variety of vertebrate species. There is increasing evidence that these sites may be hot-spots for chromosomal rearrangements, fragility and neoplasia. We have investigated whether the interstitial telomere bands found in hamster chromosomes from a human hamster hybrid cell line are hot-spots for chromosome rearrangements induced by DNA-damaging agents. Our data indicate that the interstitial telomere bands are involved in chromosomal rearrangements observed at the first mitosis after G1 exposure of cells to X-rays or restriction endonucleases at a four- to fivefold higher frequency than expected based on their size. In addition, we have extended these observations to demonstrate for the first time that these interstitial telomere-repeat-like sequences participate in the delayed chromosomal instability observed in the progeny of cells surviving X-ray-exposure at multiple generations after irradiation. In two highly unstable clones showing multiple populations of rearranged chromosomes, interstitial telomere bands were observed at the site of recombination between the human and hamster chromosomes at a five- to sixfold higher frequency than expected. There were also rearrangement and amplification of the interstitial telomere bands within the hamster chromosomes. These rearrangements occur during clonal expansion of cells surviving treatment with DNA-damaging agents and suggest a role for the interstitial telomere band in driving chromosomal instability. We conclude from the observed data that interstitial telomere bands function as recombinational hot-spots that participate in generating the diverse chromosome rearrangements observed both immediately and as a delayed effect of cellular exposure to DNA damaging agents.

Animals↗