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Coffee consumption and risk of total and cardiovascular
mortality among patients with type 2 diabetes
Bidel, S., Hu, G., Qiao, Q., Jousilahti, P., Antikainen, R. and Tuomilehto, J. Diabetologia. 2006; 49(11): 2618-26. IF 5.337 AIMS/HYPOTHESIS: Higher habitual coffee drinking has been associated with a lower risk of developing type 2 diabetes. The relation between coffee consumption and risk of cardiovascular disease (CVD) has been examined in many studies, but the issue remains controversial. This study was designed to assess the association between coffee consumption and CVD mortality among patients with type 2 diabetes. METHODS: We prospectively followed 3,837 randomly ascertained Finnish patients with type 2 diabetes aged 25 to 74 years. Coffee consumption and other study parameters were determined at baseline. The International Classification of Diseases was used to identify CHD, CVD and stroke cases using computerised record linkage to the national Death Registry. The associations between coffee consumption at baseline and risk of total, CVD, CHD, and stroke mortality were analysed by using Cox proportional hazards models. RESULTS: During the average follow-up of 20.8 years, 1,471 deaths were recorded, of which 909 were coded as CVD, 598 as CHD and 210 as stroke. The respective multivariate-adjusted hazard ratios in participants who drank 0-2, 3-4, 5-6, and >/=7 cups of coffee daily were 1.00, 0.77, 0.68 and 0.70 for total mortality (P<0.001 for trend), 1.00, 0.79, 0.70 and 0.71 for CVD mortality (P=0.006 for trend), 1.00, 0.78, 0.70 and 0.63 for CHD mortality (p=0.01 for trend), and 1.00, 0.77, 0.64 and 0.90 for stroke mortality (p=0.12 for trend). CONCLUSIONS/INTERPRETATION: In this large prospective study we found that in type 2 diabetic patients coffee drinking is associated with reduced total, CVD and CHD mortality. Time-activity relationships to VOC personal exposure factors Edwards, R. D., Schweizer, C., Llacqu, V., Lai, H. K., Jantunen, M., Bayer-Oglesby, L. and Kunzli, N. Atmospheric Environment. 2006; 40(29): 5685-5700. Article. IF 2.724 Social and demographic factors have been found to play a
significant role in differences between time-activity patterns of
population subgroups. Since time-activity patterns largely
influence personal exposure to compounds as individuals move across
microenvironments, exposure subgroups within the population may be
defined by factors that influence daily activity patterns.
Socio-demographic and environmental factors that define
time-activity subgroups also define quantifiable differences in VOC
personal exposures to different sources and individual compounds in
the Expolis study. Significant differences in exposures to
traffic-related compounds ethylbenzene, m- and p-xylene and
o-xylene were observed in relation to gender, number of children
and living alone. Categorization of exposures further indicated
time exposed to traffic at work and time in a car as important
determinants. Increased exposures to decane, nonane and undecane
were observed for males, housewives and self-employed. Categorization of exposures indicated exposure subgroups related
to workshop use and living downtown. Higher exposures to 3-carene
and a-pinene commonly found in household cleaning products and
fragrances were associated with more children, while exposures to
traffic compounds ethylbenzene, rn- and p-xylene and o-xylene were
reduced with more children. Considerable unexplained variation
remained in categorization of exposures associated with home
product use and fragrances, due to individual behavior and product
choice. More targeted data collection methods in VOC exposure
studies for these sources should be used. Living alone was
associated with decreased exposures to 2-methyl-1-propanol and
1-butanol, and traffic-related compounds. Identification of these subgroups may help to reduce the large amount of unexplained variation in VOC exposure studies. Further they may help in assessing impacts of urban planning that result in changes in behavior of individuals, resulting in shifts in the patterns of exposure experienced by the population. (c) 2006 Elsevier Ltd. All rights reserved. Jalava, P. I., Salonen, R. O., Halinen, A. I., Penttinen, P., Pennanen, A. S., Sillanpää, M., Sandell, E., Hillamo, R. and Hirvonen, M. R. Toxicology and Applied Pharmacology. 2006; 215(3): 341-353. Article. IF 3.148 The impact of long-range transport (LRT) episodes of wildfire
smoke on the inflammogenic and cytotoxic activity of urban air
particles was investigated in the mouse RAW 264.7
macrophages. The particles were sampled in four size ranges using a modified
Harvard high-volume cascade impactor, and the samples were
chemically characterized for identification of different emission
sources. The particulate mass concentration in the accumulation
size range (PM1-0.2) was highly increased during two LRT episodes,
but the contents of total and genotoxic polycyclic aromatic
hydrocarbons (PAH) in collected particulate samples were only
10-25% of those in the seasonal average sample. The ability of coarse (PM10-2.5), intermodal size range
(PM2.5-1), PM1-0.2 and ultrafine (PM0.2) particles to cause
cytokine production (TNF alpha, IL-6, MIP-2) reduced along with
smaller particle size, but the size range had a much smaller impact
on induced nitric oxide (NO) production and cytotoxicity, or
apoptosis. The aerosol particles collected during LRT episodes had
a substantially lower activity in cytokine production than the
corresponding particles of the seasonal average period, which is
suggested to be due to chemical transformation of the organic
fraction during aging. However, the episode events were associated with enhanced inflammogenic and cytotoxic activities per inhaled cubic meter of air due to the greatly increased particulate mass concentration in the accumulation size range, which may have public health implications. (c) 2006 Elsevier Inc. All rights reserved. Abstaining from alcohol and labour market underperformance - Have we forgotten the 'dry' alcoholics? Johansson, E., Alho, H., Kiiskinen, U. and Poikolainen, K. Alcohol and Alcoholism. 2006; 41(5): 574-579. Article. IF 2.040 Aims: To investigate whether abstainers fare worse than
non-abstainers on the labour market because a subset of the
abstainers are ex-drinkers with alcohol problems. Methods: In the cross-sectional population survey 'health 2000 in Finland' (n = 10 000) carried out in 2000, alcohol dependency was measured using the DSM-IV diagnostic criteria for alcohol dependence. The CIDI (composite international diagnostic interview) was applied to ascertain lifetime DSM-IV diagnoses for substance abuse diagnoses, including alcohol dependence. Individuals were considered to be employed if they were working part-time or full-time. Results: Male abstainers have on average 9.5 percentage points
lower employment probability than non-abstainers. However,
abstainers who have never drunk alcohol do not have lower
employment probability than non-abstainers. Abstainers who are
diagnosed as alcohol dependent have 27 percentage points lower
employment probability than non-abstainers. Conclusion: The underperformance of abstainers in a labour market sense is almost entirely due to the fact that some abstainers are ex-drinkers who in our study are identified as alcohol-dependent. Otherwise abstaining does not decrease employment probability. Improving the world's health--the role of National Public Health Institutes Jousilahti, P. Cent Eur J Public Health. 2006; 14(1): 3-5. Full text Kallio, R., Sequeiros, R., Surcel, H. M., Ohtonen, P., Kiviniemi, H. and Syrjälä, H. Cytokine. 2006; 34(5-6): 278-283. Article. IF 2.012 An early systemic response induced by magnetic resonance imaging (MRI)-guided interstitial percutaneous laser thermoablation was analyzed in 13 consecutive patients with malignant liver tumors by serum interleukin (IL)-1 beta, 11-6, IL-10, tumor necrosis factor (TNF)-alpha, its receptor TNFRI, and C-reactive protein (CRP) levels up to 72 It after the procedures. Only IL-6 (p = 0.033) and TNFRI (p < 0.001) increased statistically significantly after ablation, while the TNF-alpha, IL-1 beta, and IL-10 levels remained unchanged. The peak median CRP response was 92 mg/l. There was a dose-dependent correlation between the energy used and the maximum CRP values (tau = 0.68, p = 0.013). MRI-guided laser thermoablation induced an early systemic inflammatory reaction with statistically significantly elevated IL-6, TNFRI, and CRP levels but not TNF-alpha or IL-10 levels and without procedure-related complications, favoring this procedure as a safe therapeutic alternative for well-selected patients with liver tumors. (c) 2006 Elsevier Ltd. All rights reserved. Structural and functional changes in peripheral vasculature of Fabry patients Kalliokoski, R. J., Kalliokoski, K. K., Penttinen, M., Kantola, I., Leino, A., Viikari, J. S., Simell, O., Nuutila, P. and Raitakari, O. T. Journal of Inherited Metabolic Disease. 2006; 29(5): 660-666. Article. IF 1.722 Objective: Fabry disease is a lysosomal storage disorder due to
deficient alpha-galactosidase A activity, which leads to
glycosphingolipid accumulation especially in vascular smooth-muscle
and endothelial cells. Little is known about the effects of Fabry
disease on peripheral artery function and structure. Therefore, we
aimed to further characterize the peripheral vascular structural
and functional changes in Fabry disease. Methods and results: We measured structural and functional
vascular parameters, including intima-media thickness (IMT) of
brachial and carotid arteries and abdominal aorta, carotid and
aortic compliance, and brachial artery flow-mediated dilatation
(FMD) in 17 Fabry patients and 34 healthy controls matched for age,
sex and smoking. Carotid IMT (0.64 +/- 0.15 vs 0.57 +/- 0.12 mm),
brachial IMT (1.02 +/- 0.25 vs 0.74 +/- 0.18 mm), and aortic IMT
(0.31 +/- 0.09 vs 0.26 +/- 0.04 mm) were significantly increased,
and brachial FMD was significantly impaired (6.3 +/- 5.0 vs 9.7 +/-
3.9%) in Fabry patients compared to healthy controls (p < 0.05
in all comparisons after adjustments for age, LDL-cholesterol, and
systolic blood pressure). No differences were observed in arterial
compliance between the groups. Conclusions: These data suggest that Fabry disease affects arterial function and structure by disturbing peripheral endothelial function and promoting intima-media thickening. Lanki, T., de Hartog, J. J., Heinrich, J., Hoek, G., Janssen, N. A., Peters, A., Stolzel, M., Timonen, K. L., Vallius, M., Vanninen, E. and Pekkanen, J. Environ Health Perspect. 2006; 114(5): 655-60. IF 5.342 Epidemiologic studies have shown that ambient particulate matter
(PM) has adverse effects on cardiovascular health. Effective
mitigation of the health effects requires identification of the
most harmful PM sources. The objective of our study was to evaluate relative effects of
fine PM [aerodynamic diameter0.1 mV, with odds ratios at 2-day lag
of 1.53 [95% confidence interval (CI), 1.19-1.97] and 1.11 (95% CI,
1.02-1.20) per 1 microg/m3, respectively. In multipollutant models,
where we used indicator elements for sources instead of
source-specific PM2.5, only absorbance (elemental carbon), an
indicator of local traffic and other combustion, was associated
with ST segment depressions. Our results suggest that the PM fraction originating from combustion processes, notably traffic, exacerbates ischemic heart diseases associated with PM mass. Mäkelä, M., Vaarala, O., Hermann, R., Salminen, K., Vahlberg, T., Veijola, R., Hyöty, H., Knip, M., Simell, O. and Ilonen, J. Journal of Autoimmunity. 2006; 27(1): 54-61. Article. IF 2.491 Enteral virus infections may trigger the development of
beta-cell-specific autoimmunity by interacting with the
gut-associated lymphoid system. We analyzed the effect of three different virus infections on
immunization to dietary insulin in children carrying increased
genetic risk for type I diabetes. Forty-six of 238 children
developed multiple diabetes-associated autoantibodies and 31
clinical diabetes (median follow-up time 75 months).
Insulin-binding antibodies were measured with EIA method (median
follow-up time 24 months). Antibodies to enteroviruses, rotavirus
and adenovirus were measured with EIA in samples drawn at birth and
the ages of 3 and 6 months. Nineteen enterovirus, 14 rotavirus and
8 adenovirus infections were diagnosed. At the ages of 6, 12, and
18 months, the concentrations of insulin-binding antibodies were
higher in children with postnatal entero-, rota- and/or adenovirus
infections than in children without these infections. Children who
subsequently developed ICA or IA-2 antibodies or clinical type 1
diabetes had higher concentrations of insulin-binding antibodies
than children who remained autoantibody negative. Our data suggest that enteral virus infections can enhance immune response to insulin, induced primarily by bovine insulin in cow's milk. An enhanced antibody response to dietary insulin preceded the development of beta-cell specific autommumity and type I diabetes. (c) 2006 Elsevier Ltd. All rights reserved. Pajari, P. M., Jallinoja, P. and Absetz, P. Soc Sci Med. 2006; 62(10): 2601-11. IF 2.619 This study analyses arguments for and against the notion of
healthy lifestyles, and the construction of responsibility for
health, in group discussions in Finland. With data from four focus groups, we identified five
interpretative repertoires: a strong activity repertoire reflects
the dominant cultural value of health and emphasizes self-control.
Three other repertoires--illness, external barriers, and weak
character--share the underlying values of the activity repertoire,
but exemplify situations where the individual lacks control,
seeking to justify deviations from the norm of activity. One counter-repertoire, the pleasure repertoire, questions the
hegemonic value of health, and discusses other competing values.
The discussion of health is an ongoing dialectical process drawing
from the different repertoires. In order to avoid stigmatization
and to save face in the social situation of a focus group, the
subjects strive to balance their accounts of behaviours considered
unhealthy by also claiming healthy behaviours. They also strike a
balance between extreme rigidity and carelessness, emphasizing the
ideal of moderation and harmony. The findings point to a need to consider variations in and underpinnings of a "good life" at the individual level. Encouraging people to specify the meaning and content of moderation in their personal lives could provide a new perspective for health education and health promotion. Salmi, M. and Jalkanen, S. Blood. 2006; 108(5): 1555-61. IF 10.131 Vascular adhesion protein-1 (VAP-1) is a homodimeric
glycoprotein that belongs to a unique subgroup of
cell-surface-expressed oxidases. In adults, endothelial VAP-1
supports leukocyte rolling, firm adhesion, and transmigration in
both enzyme activity-dependent and enzyme activity-independent
manner. Here we studied the induction and function of VAP-1 during human
ontogeny. We show that VAP-1 is already found in the smooth muscle
at embryonic week 7. There are marked time-dependent switches in
VAP-1 expression in the sinusoids of the liver, in the peritubular
capillaries of the kidney, in the capillaries of the heart, and in
the venules in the lamina propria of the gut. Fetal VAP-1 is
dimerized, and it is enzymatically active. VAP-1 in fetal-type
venules is able to bind cord blood lymphocytes. Also, adenovirally
transfected VAP-1 on human umbilical vein endothelial cells is
involved in rolling and firm adhesion of cord blood lymphocytes
under conditions of physiologic shear stress. We conclude that VAP-1 is synthesized from early on in human vessels and it is functionally intact already before birth. Thus, VAP-1 may contribute critically to the oxidase activities in utero, and prove important for lymphocyte trafficking during human ontogeny. Scott, L. J., Bonnycastle, L. L., Willer, C. J., Sprau, A. G., Jackson, A. U., Narisu, N., Duren, W. L., Chines, P. S., Stringham, H. M., Erdos, M. R., Valle, T. T., Tuomilehto, J., Bergman, R. N., Mohlke, K. L., Collins, F. S. and Boehnke, M. Diabetes. 2006; 55(9): 2649-2653. Article. IF 8.028 Transcription factor 7-like 2 (TCF7L2) is part of the Wnt
signaling pathway. Genetic variants within TCF7L2 on chromosome 10q
were recently reported to be associated with type 2 diabetes in
Icelandic, Danish, and American (U.S.) samples. We previously observed a modest logarithm of odds score of 0.61
on chromosome 10q, similar to 1 Mb from TCF7L2, in the
Finland-United States Investigation of NIDDM Genetics study. We
tested the five associated TCF7L2 single nucleotide polymorphism
(SNP) variants in a Finnish sample of 1,151 type 2 diabetic
patients and 953 control subjects. We confirmed the association
with the same risk allele (P value < 0.05) for all five SNPs.
Our strongest results were for rs1255372 (odds ratio [OR] 1.36 [95%
CI 1.15-1.61], P = 0.00026) and rs7903146 (1.33 [1.14-1.56], P =
0.00042). Based on the CEU HapMap data, we selected and tested 12
additional SNPs to tag SNPs in linkage disequilibrium with
rs1255372. None of these SNPs showed stronger evidence of
association than rs12255372 or rs7903146 (OR <= 1.26, P >=
0.0054). Our results strengthen the evidence that one or more variants in TCF7L2 are associated with increased risk of type 2 diabetes. Suominen-Taipale, A. L., Martelin, T., Koskinen, S., Holmen, J. and Johnsen, R. BMC Health Services Research. 2006; 6. Article. IF 1.625 Background: The aim of the study was to examine gender
differences in the self-reported use of health care services by the
elderly in rural and metropolitan areas of two Nordic countries
with slightly different health care systems: Finland and
Norway. Methods: Population based, cross-sectional surveys conducted in
Nord-Trondelag Norway ( 1995 - 97) and in rural and metropolitan
areas of Finland ( 1997) were employed. In the Norwegian data, a
total of 7,919 individuals, aged 65 - 74 years old were included,
and the Finnish data included 1,500 individuals. The outcome
variables comprised whether participants had visited a general
practitioner or a specialist, or had received hospital care or
physiotherapy during the past 12 months. Gender differences in the
use of health care services were analysed by multiple logistic
regression, controlling for health status and socio-demographic
characteristics. Results: In Norway, elderly women visited a specialist or were
hospitalised less often than men. In Finland, elderly women used
all health care services except hospital care more often than men.
In Norway, less frequent use of specialist care by women was not
associated with self-reported health or chronic diseases. Conclusion: The findings revealed differences in self-reported use of secondary care among different genders in areas of Norway and Finland. Dietary insulin as an immunogen and tolerogen Tiittanen, M., Paronen, J., Savilahti, E., Virtanen, S. M., Ilonen, J., Knip, M., Åkerblom, H. K. and Vaarala, O. Pediatr Allergy Immunol. 2006; 17(7): 538-43. IF 2.126 We have shown that exposure to bovine insulin (BI) in cow's milk
(CM) formula induces an insulin-specific immune response in
infants. Here we studied the role of human insulin (HI) in breast milk as
a modulator of the immune response to insulin. In a group of 128
children participating in the TRIGR pilot study, maternal breast
milk samples were collected 3-7 days and/or 3 months after
delivery. After exclusive breast-feeding, the children received
either CM formula or casein hydrolysate during the first 6-8 months
of life. Insulin concentration in breast milk and immunoglobulin G
(IgG) antibodies to BI in plasma samples were measured by EIA. The
levels of insulin in breast milk samples were higher in mothers
affected by type 1 diabetes than in non-diabetic mothers (p = 0.007
and p < 0.001). The concentration of insulin in breast milk
correlated inversely with the plasma levels of IgG antibodies to BI
at 6 months of age in children who received CM formula (r = -0.39,
p = 0.013), and at 12 months of age in all children (r = -0.25, p =
0.029). The levels of breast milk insulin were higher in the
mothers of nine children who developed beta-cell autoimmunity when
compared with autoantibody-negative children (p = 0.030); this
holds true also when only children of diabetic mothers were
included (p = 0.045). BI in CM induces higher levels of IgG to
insulin in infants than does HI in breast-fed children. Instead, HI
in breast milk seems to be tolerogenic and may downregulate the IgG
response to dietary BI. However, our results in infants who developed beta-cell autoimmunity suggest that in this subgroup of children breast milk insulin does not promote tolerance. Mycobacteria and fungi in moisture-damaged building materials Torvinen, E., Meklin, T., Torkko, P., Suomalainen, S., Reiman, M., Katila, M. L., Paulin, L. and Nevalainen, A. Appl Environ Microbiol. 2006; 72(10): 6822-4. IF 3.818 In contrast to the growth of fungi, the growth of mycobacteria in moisture-damaged building materials has rarely been studied. Environmental mycobacteria were isolated from 23% of samples of moisture-damaged materials (n = 88). The occurrence of mycobacteria increased with increasing concentrations of fungi. Mycobacteria may contribute to indoor exposure and associated adverse health effects. Protecting our unborn children: how to measure exposure to thousands of chemicals? Tuomisto, J. Arch Dis Child. 2006; 91(8): 627-8. IF 1.787 For 30 years cancers have been the most feared diseases linked to environmental chemicals. Recently developmental effects, especially those of the central nervous system, appear to have taken their place at least in part. Both the chemicals involved and the ways of exposure are manifold. Methyl mercury, polychlorinated biphenyls (PCBs), and dioxins derive from fish. Lead comes from multiple sources, historically from leaded gasoline and paints, in some countries also from plumbing. Polybrominated diphenylethers are added to synthetic materials as flame retardants. We are exposed to pesticide residues in our food as well as in our home environment. Most of these potential new dangers are plagued with controversy. In many cases it is a question of dose. There is no doubt about the developmental neurotoxicity of lead or methyl mercury, but are the present environmental exposures high enough to cause risk? Van den Berg, M., Birnbaum, L. S., Denison, M., De Vito, M., Farland, W., Feeley, M., Fiedler, H., Hakansson, H., Hanberg, A., Haws, L., Rose, M., Safe, S., Schrenk, D., Tohyama, C., Tritscher, A., Tuomisto, J., Tysklind, M., Walker, N. and Peterson, R. E. Toxicological Sciences. 2006; 93(2): 223-241. Review. IF 3.088 In June 2005, a World Health Organization (WHO)-International
Programme on Chemical Safety expert meeting was held in Geneva
during which the toxic equivalency factors (TEFs) for dioxin-like
compounds, including some polychlorinated biphenyls (PCBs), were
reevaluated. For this reevaluation process, the refined TEF
database recently published by Haws et al. (2006, Toxicol. Sci. 89,
4-30) was used as a starting point. Decisions about a TEF value
were made based on a combination of unweighted relative effect
potency (REP) distributions from this database, expert judgment,
and point estimates. Previous TEFs were assigned in increments of
0.01, 0.05, 0.1, etc., but for this reevaluation, it was decided to
use half order of magnitude increments on a logarithmic scale of
0.03, 0.1, 0.3, etc. Changes were decided by the expert panel for
2,3,4,7,8-pentachlorodibenzofuran (PeCDF) (TEF = 0.3),
1,2,3,7,8-pentachlorodibenzofuran (PeCDF) (TEF = 0.03),
octachlorodibenzo-p-dioxin and octachlorodibenzofuran (TEFs =
0.0003), 3,4,4',5-tetrachlorbiphenyl (PCB 81) (TEF = 0.0003),
3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) (TEF = 0.03), and a
single TEF value (0.00003) for all relevant mono-ortho-substituted
PCBs. Additivity, an important prerequisite of the TEF concept was
again confirmed by results from recent in vivo mixture studies.
Some experimental evidence shows that non-dioxin-like aryl
hydrocarbon receptor agonists/antagonists are able to impact the
overall toxic potency of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
and related compounds, and this needs to be investigated further.
Certain individual and groups of compounds were identified for
possible future inclusion in the TEF concept, including 3,4,4'-TCB
(PCB 37), polybrominated dibenzo-p-dioxins and dibenzofurans, mixed
polyhalogenated dibenzo-p-dioxins and dibenzofurans,
polyhalogenated naphthalenes, and polybrominated biphenyls. Concern
was expressed about direct application of the TEF/total toxic
equivalency (TEQ) approach to abiotic matrices, such as soil,
sediment, etc., for direct application in human risk assessment.
This is problematic as the present TEF scheme and TEQ methodology
are primarily intended for estimating exposure and risks via oral
ingestion (e.g., by dietary intake). A number of future approaches to determine alternative or additional TEFs were also identified. These included the use of a probabilistic methodology to determine TEFs that better describe the associated levels of uncertainty and "systemic" TEFs for blood and adipose tissue and TEQ for body burden. Dietary factors of one-carbon metabolism and prostate cancer risk Weinstein, S. J., Stolzenberg-Solomon, R., Pietinen, P., Taylor, P. R., Virtamo, J. and Albanes, D. Am J Clin Nutr. 2006; 84(4): 929-935. IF 5.853 BACKGROUND: Folate is hypothesized to be inversely associated
with the risk of several cancers, but such a potential association
has not been well studied for prostate cancer. Vitamin B-6, vitamin
B-12, methionine, and alcohol can influence folate-related
metabolism. OBJECTIVE: The objective was to investigate the associations
between dietary factors of one-carbon metabolism and prostate
cancer risk within the alpha-Tocopherol, beta-Carotene Cancer
Prevention Study. DESIGN: Of the cohort's 27 111 Finnish male smokers aged 50-69 y
who had complete dietary data, 1270 had a diagnosis of incident
prostate cancer between 1985 and 2002. Folate, vitamin B-6, vitamin
B-12, methionine, and alcohol intakes were estimated from a
276-item modified dietary history questionnaire. Cox proportional
hazard models, adjusted for age and vitamin supplement use,
estimated relative risks (RR) and 95% CIs. RESULTS: Vitamin B-6 intake was inversely associated with
prostate cancer risk (RR for highest versus lowest quintile: 0.88;
95% CI: 0.72, 1.07; P for trend = 0.045), whereas vitamin B-12
intake was associated with significantly increased risk (RR = 1.36;
95% CI: 1.14, 1.96; P for trend = 0.01). No association between
folate or alcohol intake and prostate cancer risk was observed. No
differences were found in the above associations according to stage
of disease or subgroups of several potential effect
modifiers. CONCLUSIONS: We found no convincing evidence for a protective role of one-carbon metabolism against prostate cancer, although these observations can be generalized only to smokers. The possible modest protective association with vitamin B-6 and the significantly elevated risk with vitamin B-12 intake warrant further investigation. Yegutkin, G. G., Mikhailov, A., Samburski, S. S. and Jalkanen, S. Mol Biol Cell. 2006; 17(8): 3378-85. IF 6.520 Current models of extracellular ATP turnover include transient release of nanomolar ATP concentrations, triggering of signaling events, and subsequent ectoenzymatic inactivation. Given the high substrate specificity for adenylate kinase for reversible reaction (ATP + AMP <--> 2ADP), we exploited lymphoid ecto-adenylate kinase as an intrinsic probe for accurate sensing pericellular ATP. Incubation of leukemic T- and B-lymphocytes with [3H]AMP or [alpha-32P]AMP induces partial nucleotide conversion into high-energy phosphoryls. This "intrinsic" AMP phosphorylation occurs in time- and concentration-dependent fashions via nonlytic supply of endogenous gamma-phosphate-donating ATP, remains relatively resistant to bulk extracellular ATP scavenging by apyrase, and is diminished after lymphocyte pretreatment with membrane-modifying agents. This enzyme-coupled approach, together with confocal imaging of quinacrine-labeled ATP stores, suggests that, along with predominant ATP accumulation within cytoplasmic granules, micromolar ATP concentrations are constitutively retained on lymphoid surface without convection into bulk milieu. High basal levels of inositol phosphates in the cells transfected with ATP-selective human P2Y2-receptor further demonstrate that lymphocyte-surrounding ATP is sufficient for triggering purinergic responses both in autocrine and paracrine fashions. The ability of nonstimulated lymphocytes to maintain micromolar ATP halo might represent a novel route initiating signaling cascades within immunological synapses and facilitating leukocyte trafficking between the blood and tissues. |