Aspirin and statin medication decreases the risk of myocardial infarction associated with LTA and NFKBIL1 polymorphisms

Lymphotoxin-α (LTA) is a cytokine involved in inflammatory reactions. NFKBIL1 is a regulator of the NF-κB complex. The study investigated the associations of LTA 804 C>A and NFKBIL1-63 T>A polymorphisms with the use of statin and acetylsalicylic acid (ASA) treatment in relation to myocardial infarction (MI). The study population comprised of 600 Finnish individuals who underwent coronary angiography volunteering for the Angiography and Genes Study. Genotypes were detected by the TaqMan 5′ nuclease assay. We found a interaction between the LTA genotype (p=0.002) and the NFKBIL1 genotype (p=0.012) and statin treatment in relation to MI. Subjects with the LTA AA or the NFKBIL1 AA genotype were at a 2.77 (95% CI:1.22-6.24) and 2.85 (95% CI:1.22-6.66) times higher risk, respectively, of suffering an MI when compared to other genotypes among statin non-users. ASA treatment also modulated associations between LTA and NFKBIL1 genotypes and MI (p=0.015 and p=0.028 respectively). The NFKBIL1-A-LTA-A haplotype showed a 61% increase in the risk of MI compared to the NFKBIL1-T-LTA-C haplotype among statin non-users. Anti-inflammatory medication modifies the genotype-related risk of MI, suggesting that subjects with LTA and NFKBIL1 AA haplotype might especially benefit from the treatment.     

Increased proliferation activity measured by immunoreactive Ki67 is associated with survival improvement in rectal／recto sigmoid cancer

AIM: To assess the expression of Ki67 as prognosticator in rectal/recto sigmoid cancer. METHODS: Samples from 146 patients with rectal and recto sigmoid cancer were studied for expression of Ki67 and its prognostic significance in comparison with clinico-pathological predictors of survival. Formalin-fixed, paraffin-embedded tissues from 6 (4.1%) patients with T1,26(17.8%) with T2,94(64.4%) with T3,and 20 (13.7%) with T4 tumors were studied. Ki67 expression was determined immunohistochemically.Samples were divided according to mean value into high (>40%) and low (≤40%) expression.Areas of extensive proliferation (>50%) were defined as 'hot spot' areas. RESULTS: Hot spot areas were present in samples regardless of histopathological grade. Lower TNM and Dukes stage and higher expression of Ki67 and presence of Ki67 hot spot areas in histopathological samples were associated with better survival, whereas no association was observed with histopathological grade (P=0.78). In Cox multivariate regression analysis, significant prognostic factors were Dukes stage (P<0.001), presence of lymph node metastases (P=0.015),age(P=0.035) and presence of Ki67 hot spot areas (P = 0.044). CONCLUSION: Proliferative activity as measured by Ki67 in rectal cancer is associated with survival improvement compared with patients with low Ki67. Areas of prognostically significant increased proliferation were found independently of histopathological tumor grade.     

Children and medical research

A considerable proportion of medical treatments for children are based on estimates and assumptions rather than clinical evidence. Clinical research on children provokes intensive discussion internationally. While children are protected from the risks of clinical trials, they are hindered from receiving the benefits of pharmaceutical innovations obtained by adults. The recruitment of children into research trials is more complicated than that of adults for several reasons: 1) the physical size and relative water content of the body differs not just compared to adults but also amongst subgroups of children making the group of potential participants relatively small; 2) diseases common among adults may be rare among children and vice versa; 3) children's ability to understand the significance of a study varies and depends on the age and developmental stage of the child; and 4) depending on the level of understanding, differing views have been given on the degree of respect that should be paid to a child's right to consent, assent, or refuse to participate in a trial. We suggest that: 1) the number of children recruited in research trials should be kept as small as possible, but large enough to enable scientifically valid results; 2) special training should be made mandatory for researchers who study diseases of children; 3) children or adolescents should participate in decision-making that concerns them whenever possible; and 4) in minor procedures, the consent of just one parent is sufficient.     

Association of serotonin transporter promoter regulatory region polymorphism and cerebral activity to visual presentation of food

Recent functional magnetic resonance imaging (fMRI) studies have revealed links between genetic polymorphisms and cognitive and behavioural processes. Serotonin is a classical neurotransmitter of central nervous system, and it is connected to the control of appetite and satiety. In this study, the relationship between the functional variation in the serotonin transporter gene and the activity in the left posterior cingulate cortex (PCC), a brain area activated by visual food stimuli was explored. Thirty subjects underwent serial fMRI studies and provided DNA for genetic analyses. Subjects homozygous for the long allele exhibited greater left PCC activity in the comparison food > non-food compared with individuals heterozygous or homozygous for the short allele. The association between genotype and activation was linear, the subjects with two copies of the long allele variant having the strongest activation. These results demonstrate the possible genetically driven variation in the response of the left PCC to visual presentation of food in humans.     

Microarray image segmentation using additional dye--an experimental study

The DNA microarray technique allows monitoring the expression levels of thousands of genes simultaneously. A single DNA microarray experiment involves a number of error-prone manual and automated processes, which influence the results and have an impact on the subsequent stages of analysis. Typical problems of arrays are pinning errors while probe printing and the corruption of spots by noise patches. These errors should be detected at the time of image analysis in order to prevent the erroneous intensities from ending up in the analysis and inference stages. RESULTS: In this paper we introduce the concept (referred to as SybrSpot) of utilizing information provided by an additional dye, SYBR green RNA II, for segmentation of gene expression microarrays. Owing to the effective binding of the SYBR green RNA II to the array probes, an image with high signal-to-noise ratio is obtained. This image is used to learn about the spot quality and to flag spots which are not reliably hybridized and corrupted by noise. Further, we compare SybrSpot with GenePix and demonstrate that SybrSpot performs better than GenePix when flagging spots with no probes or weak probes. AVAILABILITY: The code is available upon request to authors.     

Structure-function correlations of growth hormone or/and prolactin-producing pituitary adenomas: an in vitro study with the reverse hemolytic plaque assay

The purpose of this study was to detect in vitro growth hormone (GH) and prolactin (PRL) secretion from adenomas clinically associated with GH or PRL hypersecretion. The reverse hemolytic plaque assay (RHPA) was applied in order to reveal possible differences among various morphologic adenoma types, and to examine the inhibitory effects of octreotide on GH release as well. The 20 surgically resected pituitary adenomas studied included 15 from acromegalic patients and 5 from patients with hyperprolactinemia. All adenomas were diagnosed by histology, immunocytochemistry and electron microscopy. Among tumors associated with acromegaly, 5 were densely granulated (DG), 5 were sparsely granulated (SG) somatotroph (SM) adenomas, 2 were mammosomatotroph (MSM) and 3 mixed somatotroph-lactotroph cell (mixed SM-LT) adenomas; tumors causing hyperprolactinemia included 4 lactotroph (LT) adenomas and 1 mixed SM-LT adenoma. GH release assessed by the RHPA corresponded to in vivo hormone secretion and to tissue immunoreactivity. Statistical analysis showed significant differences among all morphologic types of SM adenomas, exclusive of SG-SM adenomas compared to mixed SM-LT adenomas. The mean plaque size in DG-SM and MSM adenomas was significantly greater than that of SG-SM and mixed SM-LT adenomas, indicating higher GH secretion by the former two types during the same incubation time. PRL secretion was documented in 2 mixed SM-LT adenomas. Plaques for PRL, but not for GH were formed in all LT adenomas. In all SM and LT adenomas, cells producing large plaques represented a minority of the plaque-forming cell population, however, they accounted for the largest part of the total plaque area, thus the largest part of hormone secretion. Octreotide effects on GH release were studied in 6 adenomas by the RHPA. Octreotide treatment induced a rapid and significant reduction in GH secretion by SM cells in vitro, with a selective effect on high-secreting cells.     

Extended Family History of Diabetes and Autoimmune Diseases in Children With and Without Type 1 Diabetes

OBJECTIVE

To determine the extended family history of diabetes or autoimmune diseases in families with and without children having type 1 diabetes.

RESEARCH DESIGN AND METHODS

Three hundred case families and 381 control families were interviewed using structured questionnaires.

RESULTS

The proportion of case children having at least one relative with type 1 diabetes outside the nuclear family was higher than that of control children (50.3 vs. 31.8%, P < 0.001). The proportions of case and control children having relatives with type 2 diabetes or gestational diabetes were similar. Other autoimmune diseases occurred more frequently among the case children (9.7 vs. 1.1%, P < 0.001), in the case nuclear families (22.0 vs. 12.9%, P = 0.002) and in relatives outside the case nuclear family (72.0 vs. 62.2%, P = 0.007).

CONCLUSIONS

Type 1 diabetes and autoimmune diseases not only cluster in the nuclear families of children with type 1 diabetes but are also overrepresented in their extended families.First degree relatives of patients with type 1 diabetes clearly have an increased disease risk (1–5), but little information is available about the occurrence of type 1 diabetes outside the nuclear family (6). It is also unclear whether type 2 diabetes and gestational diabetes are more frequently present in the families of children with type 1 diabetes (7–9). Type 1 diabetes is known to be associated with other autoimmune diseases, but there is a scarcity of data on the frequency of autoimmune diseases among other family members (10).     

Bacteriophages fEV-1 and fD1 Infect Yersinia pestis

Bacteriophages vB_YpeM_fEV-1 (fEV-1) and vB_YpeM_fD1 (fD1) were isolated from incoming sewage water samples in Turku, Finland, using Yersinia pestis strains EV76 and KIM D27 as enrichment hosts, respectively. Genomic analysis and transmission electron microscopy established that fEV-1 is a novel type of dwarf myovirus, while fD1 is a T4-like myovirus. The genome sizes are 38 and 167 kb, respectively. To date, the morphology and genome sequences of some dwarf myoviruses have been described; however, a proteome characterization such as the one presented here, has currently been lacking for this group of viruses. Notably, fEV-1 is the first dwarf myovirus described for Y. pestis. The host range of fEV-1 was restricted strictly to Y. pestis strains, while that of fD1 also included other members of Enterobacterales such as Escherichia coli and Yersinia pseudotuberculosis. In this study, we present the life cycles, genomes, and proteomes of two Yersinia myoviruses, fEV-1 and fD1.