Altered selectivity in an Arabidopsis metal transporter

Plants require metals for essential functions ranging from respiration to photosynthesis. These metals also contribute to the nutritional value of plants for both humans and livestock. Additionally, plants have the ability to accumulate nonessential metals such as cadmium and lead, and this ability could be harnessed to remove pollutant metals from the environment. Designing a transporter that specifically accumulates certain cations while excluding others has exciting applications in all of these areas. The Arabidopsis root membrane protein IRT1 is likely to be responsible for uptake of iron from the soil. Like other Fe(II) transporters identified to date, IRT1 transports a variety of other cations, including the essential metals zinc and manganese as well as the toxic metal cadmium. By heterologous expression in yeast, we show here that the replacement of a glutamic acid residue at position 103 in wild-type IRT1 with alanine increases the substrate specificity of the transporter by selectively eliminating its ability to transport zinc. Two other mutations, replacing the aspartic acid residues at either positions 100 or 136 with alanine, also increase IRT1 metal selectivity by eliminating transport of both iron and manganese. A number of other conserved residues in or near transmembrane domains appear to be essential for all transport function. Therefore, this study identifies at least some of the residues important for substrate selection and transport in a protein belonging to the ZIP gene family, a large transporter family found in a wide variety of organisms.     

Susceptibility of skin and soft-tissue isolates of Staphylococcus aureus and Streptococcus pyogenes to topical antibiotics: indications of clonal spread of fusidic acid-resistant Staphylococcus aureus

Staphylococcus aureus (SA) isolates (n = 255) from outpatients with skin and soft-tissue infections were collected in 3 different areas in Norway. Group A streptococci (GAS, n = 68) were isolated from skin or pharyngotonsillar specimens from outpatients. Minimum inhibitory concentrations (MIC) of bacitracin, fusidic acid and mupirocin were tested using the E-test. Pulsed field gel electrophoresis (PFGE) patterns of fusidic acid-sensitive (FusS) and -resistant (FusR) SA were compared. All GAS isolates showed MIC of bacitracin of < or = 1.0 mg/l, of mupirocin of < or = 0.125 mg/l and of fusidic acid 1.0-4.0 mg/l. All the SA showed MIC of mupirocin < or = 0.5 mg/l and of bacitracin of > or = 2.0 mg/l, 91% with MIC > or = 16 mg/l. FusR was shown by 32.5% of the SA strains with similar prevalence rates in 3 different geographical areas of Norway. One particular PFGE pattern (type 1) was shown by 76% of the FusR SA. SA of type 1 belonged to phage group II and produced exfoliative toxins. Thus, the results demonstrated a high prevalence of FusR among SA causing skin infections and that this was mainly due to dissemination of clonally related FusR SA.     

Quality control in colorectal cancer screening: Systematic microbiological investigation of endoscopes used in the NORCCAP (Norwegian Colorectal Cancer Prevention) trial

Background  

Endoscopic colorectal cancer (CRC) screening is currently implemented in many countries. Since endoscopes cannot be sterilised, the transmission of infectious agents through endoscopes has been a matter of concern. We report on a continuous quality control programme in a large-scale randomised controlled trial on flexible sigmoidoscopy screening of an average-risk population. Continuously, throughout a two-year screening period, series of microbiological samples were taken from cleaned ready-to-use endoscopes and cultured for bacterial growth.     

Herpes simplex virus and risk of cervical cancer: a longitudinal,nested case-control study in the nordic countries

Human papillomaviruses (HPVs) play the major role in cervical carcinogenesis. The authors reevaluated the role of herpes simplex virus type 2 (HSV-2) in this multistage process by conducting a longitudinal, nested case-control study using 1974-1993 data and comparing the results with those from a meta-analysis of studies. A Nordic cohort of 550,000 women was followed up for an average of 5 years, after which 178 cervical carcinoma cases and 527 controls were identified. HSV-2; HPV-16, HPV-18, and HPV-33; and Chlamydia trachomatis antibodies were determined at baseline by HSV-2 glycoprotein gG-2 and HPV virus-like-particle enzyme immunoassays and by using the microimmunofluorescence method. The relative risk of cervical carcinoma was calculated by conditional logistic regression. Longitudinal studies on HSV-2 and cervical neoplasia were identified through MEDLINE (National Library of Medicine, Bethesda, Maryland), and weighted mean relative risks were calculated. Smoking (relative risk = 1.6, 95% confidence interval (CI): 1.1, 2.3) and HPV-16/HPV-18/HPV-33 (relative risk = 2.9, 95% CI: 1.9, 4.3) were both associated with cervical carcinoma. The smoking- and HPV-16/HPV-18/HPV-33-adjusted relative risks for HSV-2 were 1.0 (95% CI: 0.6, 1.7) and 0.7 (95% CI: 0.3, 1.6), respectively, for HPV seropositives. In the meta-analysis, the relative risk for HSV-2 was 0.9 (95% CI: 0.6, 1.3). In both sets of data, HSV-2 did not play a role in cervical carcinogenesis.     

Maternal age,anthropometrics and pregnancy oestriol

It has been hypothesised that oestrogen exposure in utero influences the risk for breast cancer in adult life. Although several studies report associations between breast cancer and maternal factors associated with birthweight of the offspring - a marker for antenatal oestriol exposure - little is known about the relations between maternal oestrogen levels and these factors per se. We therefore analysed the association between oestriol levels in 188 women in the 17th, 25th, 33rd and 37th weeks of pregnancy, and maternal age, prepregnancy weight, height and pregnancy weight gain.Both maternal prepregnancy body mass index and maternal height were, after controlling for infant birthweight, independently and inversely associated with oestriol levels (P = 0.0021 and P = 0.0006 respectively). We found no association between maternal age or pregnancy weight gain and pregnancy oestriol levels. These findings suggest that the previously reported associations between maternal age and maternal pregnancy weight gain and the offsprings risk of breast cancer are due to factors other than antenatal exposure to oestriol.     

Completeness and accuracy of registration of ovarian cancer in the cancer registry of Norway

Completeness of reporting and accuracy of the diagnosis of ovarian cancer from one health region in Norway to the Cancer Registry were examined. Data kept by the Cancer Registry were evaluated against discharge diagnosis data from all 8 hospitals in the health region during the period of 1987-1996. The assessment of the accuracy of the diagnosis recorded in the Cancer Registry was based on review of all medical records in the hospital setting and on slide review of all histologic diagnoses. The overall completeness of reporting ovarian cancer to the Cancer Registry was 99.6%. The organ specific completeness of registration of histologic verified ovarian cancer within the Cancer Registry was 95.3%; 0.9% was erroneously coded and 3.5% had their diagnosis changed to ovarian cancer at re-evaluation. Of all ovarian cancer cases registered at the Cancer Registry, 91% had a primary histologic diagnosis. Among 591 cases identified with a histologic diagnosis in the Cancer Registry, the accuracy of the diagnosis was estimated at 92%. Coding errors were found in 2% of these cases, while in 6% of the cases it was not possible to reproduce the original diagnosis of ovarian cancer at re-evaluation. In order to provide data of high quality for cancer surveillance a cancer registry needs several data providers, such as histopathologic laboratory reports and clinical reports. In addition, assessment of reported data through stringent quality assurance procedures within the registry are necessary for reaching a nearly 100% completeness of registration as found for ovarian cancer in the Cancer Registry of Norway.     

Circulating enterolactone and prostate cancer risk: a Nordic nested case-control study

Enterolactone, a phytoestrogen belonging to the class of lignans, is produced by the intestinal microflora from precursors in plant foods and has been implicated in protection against cancer. We study the effect of enterolactone on the risk of a subsequent diagnosis of prostate cancer. We conducted a longitudinal, nested case-control study by linkage of 3 biobanks to the cancer registries in Finland, Norway and Sweden, respectively. Enterolactone concentrations were measured by time-resolved fluoroimmunoassay in serum from 794 men who had a diagnosis of prostate cancer at a mean follow-up time of 14.2 years after blood collection and among 2,550 control men matched within each cohort for age (+/-2 years), date of blood collection (+/-2 months) and county. The median enterolactone concentrations did not differ between case and control subjects in the full study group (8.4 nmol/L [25th-75th percentile = 4.5-15.0] vs. 8.5 nmol/L [25th-75th percentile = 4.3-15.9]), nor in the national groups. Odds ratios of prostate cancer risk estimated by conditional logistic regression for increasing concentrations of enterolactone in quartiles in the full study group were 1.00 (referent), 1.21 (95% confidence interval [CI] = 0.96-1.52), 1.16 (95% CI = 0.91-1.47) and 1.08 (95% CI = 0.83-1.39). The OR estimate for the highest vs. the lowest quartile of enterolactone in separate analyses of the Norwegian, Finnish and Swedish cohort was 1.21 (95% CI = 0.91-1.60), 1.02 (95% CI = 0.59-1.76) and 0.87 (95% CI = 0.45-1.67), respectively. No support for the hypothesis that high circulating enterolactone is protective against prostate cancer was found.     

Side effects and quality of life after inadvertent radiation overdosage in brachytherapy of head-and-neck cancer

PURPOSE: By comparing our old (DP5, in use from 1978 to 1994) and new (Plato, Nucletron) dose planning system, we found that the old system underestimated doses by 20-25%. To study the possible consequences for the patients treated between 1978 and 1994, all who were still alive were invited to undergo an examination with respect to side effects and quality of life (QOL). MATERIALS AND METHODS: The degree of overdosage was calculated by comparing the isodose distribution generated on the two dose planning systems. Eighty-four patients were then invited to undergo an examination with respect to side effects and QOL. The side effects were scored according to the LENT SOMA system and QOL according to European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30), and EORTC Quality of Life Questionnaire-Head & Neck 35 (QLQ-H&N35). RESULTS: The mean overdosage of brachytherapy was 19.3%. No association was found between overdosage and side effects or QOL. For implants in the lateral border of the tongue, we found a statistically significant correlation between osteoradionecrosis and the following parameters: linear activity, total activity, dose rate, and extrapolated response dose. By multivariate analysis, only total implanted activity and the use of lead protection during brachytherapy were found to be of prognostic significance with respect to development of osteoradionecrosis. CONCLUSION: The incidence of side effects after brachytherapy at the Norwegian Radium Hospital seems to have been somewhat higher in the period under investigation than at other institutions. There may be several explanations, including the use of external beam radiotherapy before brachytherapy and departure from the Paris system among others. However, the side effects were not associated with the overdosage that was the basis for the study. As opposed to the general consensus of opinion, long-term QOL was found to be worse after brachytherapy than after external beam radiotherapy. This calls for increased awareness and a systematic prospective registration of the long-term side effects of brachytherapy.     

The effect of guided imagery and amitriptyline on daily fibromyalgia pain: a prospective, randomized, controlled trial

OBJECTIVE: The effectiveness of an attention distracting and an attention focusing guided imagery as well as the effect of amitriptyline on fibromyalgic pain was studied prospectively. METHODS: Fifty-five women with previously diagnosed fibromyalgia were monitored for daily pain (VAS) in a randomized, controlled clinical trial. One group received relaxation training and guided instruction in "pleasant imagery" (PI) in order to distract from the pain experience (n=17). Another group received relaxation training and attention imagery upon the "active workings of the internal pain control systems", "attention imagery" (AI) (n=21). The control group (CG) received treatment as usual (n=17). Patients were also randomly assigned to 50-mg amitriptyline/day or placebo. Some psychological and socio-demographic variables were also measured initially. The slopes of diary pain ratings over a 4-week period were used as the outcome measures. RESULTS: We found significant differences of the pain-slopes between the three psychological conditions (P=0.0001). The pleasant imagery (P<0.005), but not the attention imagery group's slope, declined significantly when compared with the control group (P>0.05). There was neither a difference between the amitriptyline and placebo slopes (main effects, P=0.98) nor a significant amitriptyline x psychological interaction (P=0.76). CONCLUSION: Pleasant imagery (PI) was an effective intervention in reducing fibromyalgic pain during the 28-day study period. Amitriptyline had no significant advantage over placebo during the study period.     

A novel method for in situ fixation of whale brains

A new method of in situ formalin fixation was used on 38 brains from minke whales (Balaenoptera acutorostrata). The method was developed because traditional ways of fixing brains are poorly suited to the collection of whale brains. The whole brain was preserved uncut in its meninges and then excised undamaged from the skull at a later opportunity. There was no handling of the brain in the fresh state. Fixation was started within a couple of hours post mortem. All brains were subjected to gross and light microscopy examination. The results showed that both the gross and microscopic architecture of the brains were adequately preserved, with no massive gross or histological changes due to insufficient fixation apparent. The occurrence of fixation artifacts was low. Microscopic examination showed well-preserved cells and myelin in all parts of the brain. We report the mean fixed weight of the minke whale brain as 2741 g, which is the lowest among the baleen whales. The cerebellum constituted 22% of the total brain weight, which conforms to findings in other baleen whales. This in situ method can probably be used without any particular modifications in other whale species and also in large terrestrial mammals.